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FDA vs. medical freedom
Topic: FDA vs. medical freedom (Read 3562 times)
FDA vs. medical freedom
May 04, 2007, 08:52:43 AM »
By STEVEN WALKER
May 4, 2007; Page A15
The Food and Drug Administration recently argued in the D.C. Court of Appeals that it has the power to ban meat and vegetables without violating anyone's fundamental rights. The agency chose this bizarre position in an attempt to counter arguments made by patients and their advocates in Abigail Alliance v. von Eschenbach. This groundbreaking case challenges the agency's refusal to grant access to investigational drugs, even as a last resort for terminally ill patients.
Last year, a three-judge panel decided that the FDA is violating the due- process rights of terminally ill patients by denying them access to promising investigational drugs. In response the FDA moved for a rehearing by the full court, hoping to prevent a lower court-supervised examination of whether its draconian policies actually serve a narrowly tailored compelling governmental interest. In layman's terms, this means the FDA would have to show its policies toward terminal patients are so critical to the well-being of society that they supersede (in broad and highly imperfect fashion) the fundamental right of an individual to pursue life free of undue government interference. The FDA knows their policies will not survive this test, and doesn't want the question asked.
Consider the FDA's handling of Genasense, a new drug for melanoma and chronic lymphocytic leukemia (CLL), two often terminal forms of cancer. The drug is being developed by Genta, a small, innovative company with only one approved drug and limited financial resources. Despite compelling evidence that Genasense is making progress in fighting both diseases, the FDA appears determined to kill the drug.
In the case of the melanoma application, instead of reviewing the clinical-trial data in accordance with usual methods (which showed positive results), the FDA chose a nonstandard statistical approach aimed at discrediting the results. The agency used this analysis in its briefing to its advisory committee, claiming that the drug might not be effective. The committee then relied on that information to vote against approval.
Now, Genta has found a serious mathematical error in the FDA's analysis, rendering its results meaningless. Genta is filing a complaint under the Federal Data Quality Act to correct the record. But in the meantime, the drug remains unapproved and melanoma patients continue to wait.
Genasense was also shown in a well-run, randomized clinical trial (the FDA's gold standard) to cause a complete disappearance of disease in 17% of patients with advanced CLL when combined with two older drugs. Just 7% of patients in a control group who received only the older drugs experienced similar benefit. The responders to Genasense have seen their relief last an average of 36 months, while those using other drugs saw their cancer return, on average, in 22 months.
Following these results, the Director of the FDA's cancer division, Dr. Richard Pazdur, again convened a public meeting of his advisory committee. After an agency presentation designed to elicit a negative outcome, the panel voted 7 to 3 against approval, triggering an immediate reaction of surprise and dismay among many CLL experts.
But the committee vote is less surprising if one knows that the FDA appointed several voting consultants to the committee (none of them CLL experts), and recused from the meeting the only sitting member of the committee who is an expert in CLL. Perhaps even more troubling, two of the voting committee members worked behind the scenes as undisclosed consultants for the FDA on Genasense, then without disclosure voted in the open meeting.
A shocked Genta quickly requested a meeting with the FDA to seek clarity on the agency's position, and to present additional information from patient follow-up. On the referral of an eminent leukemia expert, Genta asked if we would attend the meeting as witnesses in our capacity as patient advocates. No compensation was offered, requested or received.
Most of the meeting was consumed by getting the FDA to admit the obvious: The long-lasting, complete disappearance of CLL and its symptoms constituted "clinical benefit." Making these arguments were two cancer-medicine professors at M.D. Anderson Cancer Center, the recused ODAC member and an immediate past president of the American Society of Hematology -- all experts in CLL. None were employees of Genta and collectively represented a far more qualified advisory committee than the one that the FDA had convened.
The FDA's inane answer to the CLL experts was that the long-lasting disappearance of disease in patients taking Genasense was a "theoretical construct" and not grounds for approval.
The experts explained to the FDA that complete responses in advanced CLL patients are the medical equivalent of the Holy Grail. The FDA finally agreed, but was unimpressed with emerging data showing responders to Genasense living longer than responders in the control group.
The experts were unanimous in advising that Genasense should be approved, but the FDA was unmoved. The agency's Dr. Pazdur suggested that Genta could make the drug available as an unapproved treatment through an expanded access program -- this from a regulator fond of stating that the best way to get a drug to patients in need is through approval! In this case the agency was saying to Genta: We are not going to approve your drug, but any patient who needs it can have it so long as you give it away.
Genta responded that nonapproval would be a denial of patient access to Genasense because they could not afford to give it away in an expanded access program. Twice, Dr. Pazdur referred to that logic as a "business decision."
Less than 48 hours later, the FDA rejected Genasense. Within days Genta made a "business decision," laying off a third of its staff in a cost cutting move aimed at keeping the doors open long enough to appeal the FDA's decision. The appeal was filed in early April. Genta's announcement of the filing included a statement from one of the expert physicians: "It is puzzling that they would deny approval to a drug that met its primary and key secondary endpoint, especially since these findings were observed in the only randomized controlled trial that has ever been conducted in patients with relapsed CLL."
The FDA's handling 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.
As for the FDA's belief that their power to control us and even deny us the pursuit of life itself is unlimited under the Constitution, we can only hope the appeals court disagrees. 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.
Mr. Walker is co-founder and chief adviser for the Abigail Alliance for Better Access to Developmental Drugs . He receives no compensation for his work as an advocate, nor has he ever received compensation from any private or public-sector entity involved in drug development, approval or marketing.
Last Edit: December 17, 2007, 07:34:33 AM by Crafty_Dog
Re: FDA vs. last resort terminally ill patients
Reply #1 on:
May 14, 2007, 08:51:07 AM »
Black Wednesday at the FDA
By MARK THORNTON
May 14, 2007
May 9, 2007, should be cited in the annals of cancer immunotherapy as Black Wednesday. Within an eight-hour period that day, the FDA succeeded in killing not one but two safe, promising therapies designed and developed to act by stimulating a patient's immune system against cancer. The FDA's hubris will affect the lives and possibly the life spans of cancer patients from nearly every demographic, from elderly men with prostate cancer to young children with the rarest of bone cancers.
The dream of stimulating a person's immune system to fight his cancer is older than the modern era of cancer chemotherapy. Over a hundred years ago, Dr. William Coley at Memorial Hospital in New York City experimented with bacterial agents that appeared to have properties in stimulating immune responses against sarcoma, a cancer of the muscles and bones. Advances ebbed during the era of chemotherapy in the mid-20th century, but over the last 25 years cancer immunotherapy has received much research focus and periodic support from the biotechnology industry.
Progress and investment, however, have been unsteady as tumor shrinkages following treatment never quite translated into "hard," clinically relevant outcomes such as prolongation of the survival of the patient. Still, this type of approach remains the Holy Grail of cancer treatment. One day current treatment approaches such as surgery, radiation and chemotherapy, which often kill most but not all of a cancer, could be made obsolete by a potent immune response that eradicates the cancer cells and provides subsequent protection against return and relapse.
Thus it was remarkable that in the last several months two different biotech companies, with products utilizing two completely different cancer immune approaches, came before the FDA's Advisory Committee Meeting for judgment. The first product, Provenge, made by the Dendreon company, is a cellular therapy that tackles prostate cancer. The results of the Provenge clinical trial in men with prostate cancer who had failed all other therapies appeared before the committee that advises on cell-based cancer products for the FDA Center for Biologics. This committee was comprised of immunology and oncology experts. The second product, Junovan, made by the IDM company, was tested in children with osteosarcoma, a rare bone cancer that affects just 900 children per year. The results of the Junovan clinical trial appeared before a different committee -- one that judges protein cancer agents and was comprised solely of oncologists with no immunology experts.
Both the Provenge and Junovan clinical trials provided evidence that patients lived longer compared to control groups. But according to the FDA, these "survival advantages" that statisticians talk about had "issues." When the issues were discussed in the Provenge public meeting the majority of the committee (in a 13-4 vote) thought the issues, while relevant and important, were superseded by the solid immunology science behind the product.
However, those voting in the minority, very powerful members of the oncology community, launched an unprecedented PR campaign accusing those in the majority of incompetence and naiveté in matters relating to cancer products. The arrogance of this campaign overlooked the notion that survival data from immune-based products may be qualitatively different from, and may need to be judged by different criteria than, survival data from chemotherapy drugs.
But such intriguing academic discussions never had a chance to take root. Instead -- just a few weeks after the favorable ruling on Provenge -- the Junovan product came before the FDA's Advisory Committee for approval. Incredibly, the improvement in the survival rate of children with bone cancer who received Junovan was summarily dismissed as irrelevant by the committee. Why? The statistical data showing the odds of efficacy were 94% surety instead of the usual goal of 95% surety. This 1% difference was all the committee needed to justify a 12-2 "No" vote.
The Junovan meeting was chaired by the very physician who launched the PR campaign against Provenge. Unlike the meeting on Provenge, however, all discussion time on Junovan was spent kneeling before the altar of statistics -- not a single comment was made about the immunology science supporting the efficacy of Junovan. Remarkably, as the Junovan vote was taking place, the FDA folded under the pressure and announced that it would not abide by the favorable vote on Provenge. Instead, the FDA called for more testing that -- if the product is not killed outright by its maker Dendreon -- will take at least three years to complete.
In the span of eight hours, the dawn of a new era in cancer immunotherapy was driven back into the night. It will be years before we know the full impact of these decisions and how many cancer patients, young and old, have had their lives cut short as a result. For now, however, one thing is clear: While our lawmakers obsess over FDA "safety reforms," no one is holding this government agency accountable for its complicity in stalling therapies for life-threatening diseases.
Dr. Thornton, a former medical officer in the FDA Office of Oncology Products, volunteers as president of the Sarcoma Foundation of America.
Re: FDA vs. last resort terminally ill patients
Reply #2 on:
August 08, 2007, 07:14:51 AM »
Court Rejects the Right to Use Drugs Being Tested
By ANDREW POLLACK
Published: August 8, 2007
A federal appeals court ruled yesterday that patients with terminal illnesses do not have a constitutional right to use medicines that have not yet won regulatory approval.
The 8-to-2 decision by the Court of Appeals for the District of Columbia Circuit came in a closely watched and emotional case that pitted desperate patients willing to try unproven, even risky, therapies against those arguing that drugs should be proved safe and effective before they are made available.
The decision preserves the current regulatory system. If it had gone the other way “it would have undermined the entire drug approval process,” said William B. Schultz, a former deputy commissioner of the Food and Drug Administration, who wrote an amicus brief arguing against the early access to drugs.
The case was filed against the Food and Drug Administration in 2003 by the Abigail Alliance for Better Access to Developmental Drugs, a group founded by a man whose daughter Abigail died from cancer after a long battle to receive treatment with experimental drugs that were eventually approved.
The group, joined by the Washington Legal Foundation, argued that forcing patients to wait years for a drug to go through the process of clinical trials deprived dying patients of their right to self-defense and violated the Fifth Amendment clause stating that people cannot be deprived of life, liberty or property without due process of law.
A district court ruled against the Abigail Alliance. That decision was reversed by an appeals court panel, but the full appeals court yesterday upheld the original district court decision.
Judge Thomas B. Griffith, writing for the majority, said a right to experimental drugs was not deeply rooted in the nation’s history and tradition. Judge Griffith said the right of self-defense “cannot justify creating a constitutional right to assume any level of risk without regard to the scientific and medical judgment expressed through the clinical testing process.”
In a dissent, Judge Judith W. Rogers wrote that it was “startling” that the “right to try to save one’s life is left out in the cold,” not protected by the due process clause of the Constitution, “despite its textual anchor in the right to life.”
Frank Burroughs, the founder of the Abigail Alliance, said his group was “dumbfounded that most of the justices tragically missed the merits of the case.” Mr. Burroughs vowed to appeal to the Supreme Court.
While critics often accuse the F.D.A. of letting unsafe drugs on the market, this case points to pressure on the agency from the opposite direction — patients who say it is too stringent in approving drugs for serious diseases. Many prostate cancer patients and advocacy groups, for instance, have recently criticized the agency for not approving a drug called Provenge.
The agency sometimes does lower the bar for approval of medicines for life-threatening diseases. And the companies developing such drugs can make them available before approval under some circumstances.
But Mr. Burroughs said such programs were inadequate. His organization advocates that drugs be made available to terminally ill patients as early as the conclusion of the first of three phases of clinical trials.
Some drug companies, doctors and other patient groups oppose that idea. Mr. Schultz, for instance, filed his brief supporting the current system on behalf of the National Organization for Rare Disorders, a patient advocacy group.
He and others say that if drugs were made available after only preliminary testing, drug companies would have little incentive to conduct full clinical trials to determine if a drug really works. That would allow companies to “profit from offering empty hope,” said Robert Erwin of the Marti Nelson Cancer Foundation, a patient advocacy group.
The New Right to Life
Reply #3 on:
August 10, 2007, 08:23:26 AM »
The New Right to Life
By ROGER PILON
August 10, 2007; Page A11
The wheels of justice turn slowly, especially for the dying. On Tuesday the D.C. Circuit, sitting en banc, reversed a 15-month-old decision by a panel of the court that had recognized a constitutional right of terminally ill patients to access potentially life-saving drugs not yet finally approved by the Food and Drug Administration. Given the poor quality of Tuesday's opinion in Abigail Alliance for Better Access to Developmental Drugs v. Eschenbach -- "startling," said the dissent -- one wonders why it took so long. The opinion's one virtue is that it brings out clearly how far modern "constitutional law" has strayed from the Constitution, a document written to protect liberty, not federal regulatory schemes.
Represented by the Washington Legal Foundation, Abigail Alliance is named for Abigail Burroughs, a 21-year-old college student who died of cancer in 2001. Their argument could not be more simple or straightforward, nor could Tuesday's dissent, written by Judge Judith Rogers and joined by Chief Judge Douglas Ginsburg, the majority in the earlier opinion. Citing the Fifth Amendment's right to life, the Ninth Amendment's assurance to the Constitution's ratifiers that the rights retained by the people far exceed those named in the document, and the Supreme Court's "fundamental rights" jurisprudence, Judge Rogers argued that the right to life, the right to self-preservation, and the right against interference with those rights -- which the FDA is guilty of -- are of one piece. They are deeply rooted in common law and the nation's history and traditions, implicit in the concept of ordered liberty, and thus "fundamental."
Indeed, it is startling, she noted, that the rights "to marry, to fornicate, to have children, to control the education and upbringing of children, to perform varied sexual acts in private, and to control one's own body have all been deemed fundamental, but the right to try to save one's life is left out in the cold despite its textual anchor in the right to life." Because the rights at issue here are "fundamental," she concluded, the court must apply, in judicial parlance, "strict scrutiny." The burden is on the FDA to show why its interference is justified -- to show that its regulatory interests are compelling and its means narrowly tailored to serve those interests.
There, precisely, is where Tuesday's majority demurred. In a long footnote, Judge Thomas Griffith, who had dissented in the earlier opinion but wrote now for the majority, recast the right at issue as "the right to access experimental and unproven drugs in an attempt to save one's life." Through such "tragic wordplay," as the dissent put it, the right ceases to be "fundamental," under Supreme Court precedents, because it is "not deeply rooted in the Nation's history and traditions."
So described, the right is not "deeply rooted," of course, because the very idea of "experimental and unproven drugs" implies a regulatory regime like the FDA, and that is a recent development. Yet as the dissent detailed, for most of our history individuals were free to take whatever drugs they wanted without a doctor's prescription. It was only in 1951 that Congress created a category of prescription drugs. Then in 1962 it began requiring drug companies to conduct extensive tests to ensure drug "efficacy," which led to long delays for drug approval and to the deaths of countless patients who would gladly have borne the unknown risks for a chance at life.
As a legal matter, what Judge Griffith achieved with his linguistic legerdemain was a shift in the burden of proof: No longer would the government need to justify its restrictions; the dying would have to try to overcome those restrictions. But that would be impossible because now the court would no longer strictly scrutinize the government's rationale. Rather, it would apply a "rational basis" test under which the government would win as long as it had any reason for restricting access. Deference so complete, the dissent noted, amounts to nothing less than "judicial abdication."
Plainly, the issues here go well beyond this case, which is doubtless why the court decided to rehear it en banc. And they go beyond liberal and conservative as well, as the mixed seven who joined Judge Griffith's opinion should indicate. What we have here, arguably, is a revolt of sorts by Judge Rogers and Chief Judge Ginsburg against what passes today for "constitutional law." Reducing that revolt to a simple question: Under a Constitution that expressly protects the right to life, how did we get to where government can effectively restrict the right, and the courts will do nothing?
The answer for liberal jurists is simple. Since the Progressive Era they've worked assiduously to create the modern redistributive and regulatory state, constitutional impediments notwithstanding. Following Franklin Roosevelt's infamous 1937 threat to pack the Supreme Court with six new members, the Court facilitated that agenda by distinguishing "fundamental" and "nonfundamental" rights, protected by "strict scrutiny" and "rational basis scrutiny" respectively. That invention opened the floodgates to ever-expanding legislative schemes. But liberals didn't always win in the legislatures, so they turned increasingly to the courts, urging judges to find "fundamental" rights by consulting "evolving social values."
That led to a conservative backlash and a call for "judicial restraint," especially after the Court found a fundamental "right" to abortion in 1973. Both sides, therefore, have reasons to urge judicial restraint and deference to the administrative state. Modern liberals don't want judges interfering with the legislative creation of the welfare state's social and economic rights. Conservatives hope to frustrate those legislative efforts while forestalling the judicial creation of such rights. Thus, they urge judges to protect only those rights found expressly in the Constitution -- and will describe rights, as here, to avoid even the hint of judicial activism.
In a word, then, liberal jurists could rule against Abigail Alliance to ensure the dominance of the regulatory regime. Conservative jurists, viewing that regime as "settled law," could do likewise to avoid even the appearance of judicial activism. The approach of liberals is understandable: Long ago they abandoned the written for the "living" Constitution, which enables ad hoc adjudication, the rule of law notwithstanding. The approach of conservative "originalists," however, is less easily explained, since they purport to take the Constitution seriously.
Yet in Robert Bork's "The Tempting of America," where conservatives often turn, we find an answer. Describing what he calls the "Madisonian dilemma," Judge Bork writes that America's "first principle is self-government, which means that in wide areas of life majorities are entitled to rule, if they wish, simply because they are majorities. The second principle is that there are nonetheless some things majorities must not do to minorities, some areas of life in which the individual must be free of majority rule." (emphasis added)
That turns Madison on his head. James Madison stood for limited government, not wide-ranging democracy. His first principle was that in wide areas individuals are entitled to be free simply because they are born free. His second principle was that in some areas majorities are entitled to rule because we have authorized them to. That gets the order right: individual liberty first, self-government second, as a means for securing liberty.
Yet we repeatedly see conservative jurists, as here, ignoring the true Madison -- deferring to the legislature when their duty, as Madison put it, is to stand as "an impenetrable bulwark against every assumption of power in the legislative or executive." A perfect example is Justice Antonin Scalia's dissent in a 2000 case, Troxel v. Granville, which found that Washington State's grandparent visitation act violated the right of fit parents to control access to their children. Dissenting, Justice Scalia argued that although the parental right is among the unalienable rights proclaimed by the Declaration of Independence and the unenumerated rights retained pursuant to the Ninth Amendment, that amendment does not authorize "judges to identify what [those rights] might be, and to enforce the judges' list against laws duly enacted by the people." Thus, just as the Abigail Alliance majority did, he would defer to the legislature to tell us what those rights are -- the very legislature that had extinguished the parental right that he had just located in the Ninth Amendment.
The problem with that view, of course, is that it renders the Ninth Amendment a nullity -- hardly what an originalist wants. Moreover, while recognizing retained unenumerated rights as "constitutional," it reduces them to a second class status since they are unenforceable. And that means they are not rights at all since rights are invoked, in the political context, only defensively, against threats from the majority. Yet on this view they can be extinguished by a mere majority.
There is, of course, no bright line between enumerated and unenumerated rights. In interpreting the Constitution, inferences are essential. As Judge Rogers put it, "were it impermissible to draw any inferences from a broader right to a narrower right, nearly all of the Supreme Court's substantive due process case law would be out of bounds." The only question, therefore, is whether the inferences are drawn correctly, and from sound underlying principles. To do that well, however, judges must have a sure grasp of those principles. That is the main problem today, as Tuesday's decision illustrates. The Framers would be appalled to see federal bureaucrats standing between dying patients and the medicines that might save them -- sanctioned by a Constitution turned upside-down. Fortunately, this case will be appealed and the Supreme Court may yet examine it afresh.
Mr. Pilon is vice president for legal affairs at the Cato Institute and director of Cato's Center for Constitutional Studies.
Re: FDA vs. last resort terminally ill patients
Reply #4 on:
August 14, 2007, 09:50:48 AM »
The FDA's Deadly Track Record
By RONALD L. TROWBRIDGE and STEVEN WALKER
August 14, 2007; Page A17
Last week, the full D.C. Circuit Court of Appeals reversed an earlier decision by its own three-judge panel and ruled 8-2 against a dying patient's right to pursue life by taking investigational -- but as yet FDA-unapproved -- drugs.
The case was filed in 2003 by the Abigail Alliance for Better Access to Developmental Drugs and the Washington Legal Foundation. We argued that terminal patients with no options left but death have a constitutional right to such therapy in the care of a qualified physician.
The Alliance began pushing for access to investigational drugs for terminal patients after its founding in mid-2001 upon the death of Abigail Burroughs, who was denied an investigational drug (Erbitux) that an early trial showed might have helped her. She and her doctor were right, but she never got the drug.
Over the past five years, the Alliance has pushed for access to 12 exceptionally promising investigational cancer drugs which have subsequently been approved by the FDA and now represent standard care. At the time we began our advocacy, each of the drugs had cleared at least preliminary Phase 1 testing, and in some cases more-advanced Phase 2 or Phase 3 trials. In other words, they obviously worked for some patients.
Gleevec set a tragic standard for loss of life at the hands of FDA bureaucrats. Coming out of Phase I testing in 1998, it was known beyond any reasonable doubt to be safe and effective. The Alliance started requesting access to the drug for chronic myelogenous leukemia (CML) patients in June 2001. By the time FDA approved Gleevec in March 2003, approximately 3,600 patients had been denied access to the drug. Many died waiting. More than 80% of the small number of patients who got Gleevec in clinical trials before the drug was approved are alive today.
Eloxatin, for advanced colorectal cancer, was summarily rejected by the FDA in March 2000 despite its being approved in at least 29 other countries. In January 2002, we started to ask the FDA to allow patients access. The agency delayed approval until August. In between, about 40,000 Americans died without ever getting the drug.
Erbitux, for the treatment of colorectal and head and neck cancers, was rejected by FDA in December 2001 when the agency refused to review the sponsor's application. The Alliance had begun asking the FDA to allow patient access to the drug six months earlier. The FDA delayed approval until February 2004. Almost 179,000 people with colorectal and head and neck cancer died waiting.
The Alliance began working for access to Revlimid, for multiple myeloma and myelodysplastic syndrome, in June 2002. Patients had to wait until December 2005 for FDA approval. Nearly 74,000 patients with these terminal cancers died without ever getting Revlimid.
The Alliance asked that patients get access to Velcade in June 2002. Curiously, the FDA points to this drug as proof it can work fast, but they didn't approve it until May 2003. At the time, trial results suggested that only about 25% of multiple myeloma patients should get the drug (since shown to be too low), but even with that limitation, about 2,600 patients died without ever getting Velcade.
Beginning in June 2004, we started pushing the FDA to make Nexavar and Sutent, both highly promising drugs for kidney cancer, available. The agency eventually approved Nexavar in December 2005 and Sutent in January 2006. But that was only after evidence of efficacy so compelling emerged for Nexavar that the trial demanded by the FDA -- in which dying kidney cancer patients seeking the drug were being given no other choice (except certain death from their cancer) but to agree to a 50/50 chance of being blindly randomized to a sugar pill -- was stopped by Bayer for ethical reasons and the placebo patients allowed to get the drug. The sponsor seeking approval for Sutent was given a similar option by FDA if it wanted its drug approved. About 20,000 kidney cancer patients died waiting for both drugs.
The Alliance began its push for availability of Avastin for multiple cancers in June 2002. FDA finally approved this obviously effective cancer drug in February 2004. It is now approved for colorectal and lung cancers, and being successfully used off label for several more. Almost 360,000 patients with lung and colon cancer died without ever getting Avastin.
Tarceva is used for patients with lung cancer. We began pushing for its availability in June 2001, the FDA approved the drug in November 2004. In the interim, 531,000 people with lung cancer died. Tarceva also extends the effectiveness of an existing drug for pancreatic cancer, and about 102,000 patients died from that disease during the FDA's delay.
In June 2002 we started pushing for availability and approval of Bexxar for non-Hodgkin's lymphoma. FDA, after rejecting and delaying this highly effective drug repeatedly over several years, finally approved it under intense pressure from oncologists in June 2003. About 26,000 died during the delay without ever getting the chance to try the drug. The FDA's regulatory hatchet job on Bexxar prior to its approval has caused the drug to be dramatically underused, extending the damage done by the agency's intransigence and incompetence.
In June 2002 we began our efforts to gain access to Alimta for lung cancer patients. FDA didn't approve it until February 2004. In the interim, approximately 249,000 lung cancer patients died without the chance of trying this drug to see if it would control their disease or extend their life.
The alliance started working for access to Tykerb for breast cancer in June 2004 but the FDA didn't approve the drug until March 2007. About 25% of breast cancers include the biomarker predictive of benefit from Tykerb; nearly 28,000 women who had this marker died from their cancer waiting for Tykerb. They would, according to the FDA, have each lived an average of eight months longer. Long enough, perhaps, to see a child graduate from college or get married, or to meet a new grandchild.
In sum, these 12 drugs -- had they been available to people denied entry to clinical trials -- might have helped more than one million mothers, fathers, sons and daughters live longer, better lives. We have actually underestimated the number of "life-years" lost at more than 520,000, because we have not included other safe and effective uses of these drugs that the FDA has yet to approve.
Recently, it was decided that Provenge (another drug we have been trying to get for years) will be kept away from prostate cancer sufferers for up to three more years. The reason for the delay? A small but aggressive club of FDA advisers hand-picked by the director of the agency's Office of Oncology Drug Products, Dr. Richard Pazdur, think the statistics are not yet perfect enough.
Recently, the FDA responded to our lawsuit by proposing "new" regulations governing access to investigational drugs. They propose to change nothing.
The American Cancer Society reports that some 550,000 cancer patients die annually, making the number of cancer deaths from 1997 to 2005 about 4.8 million. Over that same period, the FDA reports granting individual access to an investigational drug to not more than 650 people per year for all diseases and drugs -- a pathetic, even cruel, pittance. A few thousand more patients managed to gain access by enrolling in relatively small clinical trials or exceedingly rare expanded access programs.
The other 4.7 plus million cancer patients, not to mention millions more with other diseases, were abandoned to die, denied access to progress by their own FDA when they needed it most.
We will appeal the decision in Abigail Alliance v. Eschenbach to the Supreme Court, and agree with only one thing in the majority opinion. Congress should pass our pending legislation, called the Access Act, now. It should be added to the FDA reauthorization bill headed for a vote in September.
This is massive human tragedy, made even worse by the fact that it didn't and doesn't have to be this way. Looking at FDA automatons and the D.C. Circuit Court brings to mind T. S. Eliot's question, "Where is the wisdom we have lost in knowledge?"
Messrs. Trowbridge and Walker volunteer, respectively, as adjunct scholar and chief adviser to the Abigail Alliance for Better Access to Developmental Drugs. Mr. Walker also is co-founder of the Abigail Alliance.
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Re: FDA vs. medical freedom
Reply #5 on:
December 17, 2007, 07:36:09 AM »
Stop the War on Drugs
By SCOTT GOTTLIEB
December 17, 2007; Page A21
In December 2005, Eli Lilly & Co. pled guilty to a criminal indictment from the Bush Justice Department and paid $36 million in fines and "disgorgement" of its ill-gotten gains. The company's crime was mounting a concerted effort to inform doctors that, according to leading medical authorities, the firm's estrogen-modulating drug Evista substantially reduced the risk of invasive breast cancer in postmenopausal women.
The finding came from a series of landmark national studies, some eventually touted by government research. So why the criminal charge?
At the time Eli Lilly was conveying the cancer information to doctors, the Food and Drug Administration had approved Evista for treating osteoporosis, not preventing cancer. Only this past September -- eight years after the first significant cancer prevention results were published -- did the FDA approve Evista for use against breast cancer, turning Eli Lilly's speech "crime," by some measures, into a public service.
For patients and doctors who rely on the latest clinical information to make hard decisions, no relevant scientific discovery took place between the medical findings, the legal prosecution, and the FDA's approval of those same results. In fast moving fields like cancer, where doctors tailor treatments based on evidence that's constantly evolving, two years can be an eternity of waiting to learn about important science. For some patients, that interval can be fatal.
At issue is what's referred to as "off-label promotion" -- allegations that drug companies "encourage" doctors to use medicines for purposes not yet approved by FDA. These charges are applied even when the information drug firms are sharing is part of educational meetings, peer review journal articles or treatment guidelines issued by medical-specialty societies and government researchers.
The prosecutions are aimed at recouping federal money. The argument is that the medical community is goaded by the drug companies into filing "false claims" with the government, where hospitals and health plans charge Medicare and Medicaid for drugs used for unapproved indications.
Drug firms tend to settle these cases. Firms have good reason to cut a deal: If they fight and lose in court, they can be banned from doing any business with government programs like Medicare. At one time, prosecutions were aimed at a handful of bad actors who encouraged prescriptions for purposes far outside popular medical practice. But like a lot of government efforts, the scope of these prosecutions expanded to encompass a much broader slice of medical activity.
The Justice Department rarely alleges in these cases that the scientific information is false or misleading, only that a firm can be "ahead of the science" in sharing with doctors information about emerging uses of medicines, even when those new uses quickly become the mainstay of care. Underlying this, of course, is a nagging presumption that doctors can't be trusted to weigh for themselves this sort of medical information, and thus need the FDA's supervision.
This might be more tolerable in a world where the FDA rapidly adjudicates study results to decide what belongs in and out of drug labels. In reality, the FDA reserves 10 months to consider supplemental uses for marketed drugs, and the entire process usually is much longer. In many cases, doctors don't easily learn about these new drug uses, or get targeted education on prescribing, without the role of the drug firm that is the only deep-pocketed actor with an incentive to share this kind of information.
The Philadelphia U.S. Attorney's Office has waged a multiyear investigation into the biotech company Genentech. They are alleging that meetings the company sponsored for oncologists in the 1990s were illegal -- because Genentech shared information about unapproved uses for its drug Rituxan, used largely in the treatment of lymphoma. Never mind that the forms of lymphoma for which Rituxan was to be used were largely fatal, that some of those uses are now approved by the FDA, or that the education was based on findings from large studies, including one supported by the government. In fact, if you queried the National Cancer Institute's Web site -- even at the time when Genentech allegedly engaged in the illegal educational activity -- for advice on the best treatments for some of these same forms of lymphoma, the search returned "Rituxan."
"Off label" are now dirty words in conventional lexicon, made synonymous with lawbreaking as a result of these prosecutions, even though these words describe the way more than half of cancer medicine is practiced. It is true that some off-label drug use is based on very unsettled science and has more risks. But medicine -- and not just cancer care -- involves lots of hard choices. And the more serious the disorder, often the more likely it is that for every right and wrong treatment choice there are many other practical decisions painted in shades of gray. Efforts to confine patients and doctors to FDA-approved uses have their own health consequences, raising the question: Just who is in the best position to make these hard choices?
The travails of another Genentech drug, the breast-cancer medicine Herceptin, demonstrate the health consequences of these prosecutions. Herceptin was widely used in advanced breast cancers for years, and recently it was found to cut recurrence by about half in some patients with earlier-stage tumors. The results were first published early in 2005, and the new use was approved by the FDA in late 2006. The wider use of Herceptin will save lives, but doctors didn't embrace it right away.
Herceptin prescriptions spiked when the study was first published in the New England Journal of Medicine, only to tail off before spiking again at the time of FDA approval. Those early adopters were probably familiar with the drug and the findings, perhaps through practicing in busy academic centers. Some of the late adopters might have been reluctant to take up the new use without the benefit of targeted education. You can bet that folks at Genentech, living under the thumb of the Philadelphia U.S. attorney, weren't about to talk up the landmark findings.
The use of Herceptin in early-stage breast cancers was roughly half what you'd expect for the almost two years between publication of the study's findings and the FDA nod. It's hard to deny that some of those Herceptin-eligible women who didn't get the drug are now unnecessarily doomed.
Attorney General Michael Mukasey could add to the staff manual for his attorneys a requirement that they merely check with a public health authority like the National Institutes of Health to see if a certain "off-label" use falls within the scope of appropriate medical care before waging a legal war. Even that may be a hard sell in Washington, where prosecutions are pursued on the basis of how much money they can recoup.
This month Rep. Henry Waxman took umbrage at a copy of a draft FDA guidance (he leaked it himself) saying that, as a public health matter, the FDA found it appropriate for drug firms to share study reprints from peer reviewed medical journals. Drug firms are persona non grata in Washington, a result of the industry's own excesses, but also of a lot of political targeting. The result is an anything-that-bashes-pharma goes mentality in policy making.
Politicians wage broad wars on medicine to claim thin strips of ideological terrain. This would be good political theater if there weren't so many human victims.
Dr. Gottlieb, a practicing physician and resident fellow at the American Enterprise Institute, was deputy commissioner of the FDA from 2005 to 2007.
Re: FDA vs. medical freedom
Reply #6 on:
February 21, 2008, 08:26:39 AM »
A Moral Test for the FDA
February 21, 2008; Page A16
Some 40,000 women died from breast cancer in 2007. Almost unbelievably, the federal government may block one of the disease's more promising therapies for no other reason than the Food and Drug Administration's obsolete, even antimodern, regulations and approval models. Since the lives of terminally ill patients are in the balance, this is fundamentally a moral test -- and one, true to type, that the FDA may well flunk.
At issue is the biologic medicine Avastin, which interferes with the growth and spread of tumors through the body by choking off their blood supply. Manufactured by Genentech, Avastin was approved for colorectal cancer in 2004 and lung cancer in 2006, and it's been shown effective for treating recurrent or metastatic breast cancer. But in December, the FDA's Oncologic Drugs Advisory Committee voted 5-4 against approval. The FDA is not bound by such decisions but usually follows them, and a final ruling is expected by Saturday.
A denial in this case would not only be unscientific but unethical. It's not as though the panel or the larger FDA bureaucracy don't recognize or acknowledge Avastin's real benefits. Rather, the FDA's lords of medicine may conclude that those benefits don't matter. And they don't matter, as the panel argued, because they don't fall into the categories that the FDA generally uses to evaluate the safety and efficacy of a drug.
In clinical trials, Avastin demonstrated the longest reported "progression-free survival" for patients with advanced breast cancer. That means they live longer before their disease spreads or worsens. An initial study submitted to the FDA showed that Avastin in combination with Taxol (another cancer therapy) delayed the growth of tumors by about 11 months -- some five and half months longer than Taxol alone. Additionally, more than twice as many patients experienced significant tumor shrinkage.
In February, Genentech also released the preliminary findings of a more rigorous follow-up study, including the FDA's "gold standard" of randomized and placebo-controlled clinical trials. It again confirmed that Avastin improves progression-free survival, though the full results have not yet been made public.
In other words, dying patients live nearly twice as long on average before their disease gets worse, and maybe longer. It translates into an improvement in quality of life by delaying the onset of symptoms. But only in a few isolated contemporary cases has the FDA deemed progression-free survival as a relevant "end point" for approval. There's no reason besides the FDA's complacency and archaic procedures; a recent review by the agency's own Science Board concluded that "evaluation methods have remained largely unchanged over the last half-century."
Extending life is the FDA's acid test for any anticancer agent, but studies designed to prove it take years and thousands of patients to get large average effects. In the Avastin study, women lived slightly longer, a median of 26.5 months compared with 24.8 with Taxol alone. But those results weren't proved statistically significant to FDA satisfaction. Advanced therapies, however, often prove more effective among targeted populations and in some patients over others. Perhaps that's why, as the Journal's Marilyn Chase reported yesterday, even two members of the oncology panel may recant their nay votes.
At the very least, approval criteria should be broadened beyond crude mortality rates. Between the 1950s and early 1980s, when the treatments for cancer were far more limited, the FDA considered the response of tumors to treatment adequate to make judgments. Some of the most important chemotherapy drugs for cancer and autoimmune diseases gained approval during that period -- cyclophosphamide, tamoxifen and others. Many are still used today, including to treat breast cancer. But it took years, sometimes decades, to learn how to use and dose them effectively once they were on the market.
No doubt thousands of lives were saved or improved by such trial and error, which is another name for medical progress. That's precisely what the FDA's bureaucratic culture, led by oncology drug chief Richard Padzur, is now obstructing. Another major culprit is political pressure from Congress, where Members know they can always get headlines by calling for a crackdown on Big Pharma or exploiting public safety anxieties. Never mind patient interest.
* * *
Patients with limited options shouldn't be denied drugs that may improve what life they have left, even if it doesn't extend life in the end. Thousands of breast-cancer sufferers, on the advice of their oncologists, are currently taking Avastin "off label," and an adverse FDA decision this week will make it far more difficult for them to do so. It would also be the latest moral indictment of everything that's wrong with the FDA.
Reply #7 on:
March 30, 2011, 06:30:09 AM »
How does a device like MelaFind come into the world? It begins when a small defense contractor specializing in computer vision is approached by pharmaceutical giants seeking objective ways to evaluate unguents for hair growth, wrinkle reduction or wound healing. An adviser to the small company, a world-famous dermatologist, pipes up: "Wound healing is cool, but if you really want to do something for humanity, help us detect melanomas."
America having great capital markets, it's possible to raise $130 million for a speculative venture. The company, now called Mela Sciences, recruits Dr. Joseph Gulfo as CEO, thanks to his past successes before the Food and Drug Administration. He gives investors an extra shot of confidence by negotiating a binding "protocol agreement" with the FDA detailing how the device should proceed to approval.
MelaFind is a handheld scanner meant to provide an objective aid to doctors applying the standard visual tests for melanoma, to help make those close calls that, when called wrong, can have disastrous consequences for a patient. Because melanoma is such a killer, doctors tend to biopsy every skin flaw that looks suspicious but they still miss one melanoma for every three or four they catch.
In a clinical trial involving 23 practitioners around the country, MelaFind caught 98% of melanomas among the targeted suspicious lesions, while equaling or besting the top docs in avoiding unnecessary biopsies. Put another way: Doctors would have to greatly increase their rate of unnecessary biopsies to match MelaFind in catching melanomas.
In 9% of lesions, MelaFind couldn't capture an adequate image and refused to render a verdict. One in six of these lesions, subsequent biopsy showed, were melanomas.
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.When an FDA advisory panel met in November to review the device, the experts narrowly voted eight-to-seven in favor, with several naysayers saying they held back only on concern that MelaFind wouldn't be restricted to dermatologists. Just a few minutes earlier, Dr. Gulfo had explained to the panel that the company had wanted to limit the device to dermatologists but the FDA objected "because the FDA cannot regulate dermatologists."
One panelist also worried that the study findings were "biased" because practitioners themselves had decided which lesions raised enough concern to warrant inclusion. A perfect study undoubtedly would have subjected random patches of skin to MelaFind to see how well it could distinguish a melanoma from a Dale Earnhardt tattoo. Such a study, to find any melanomas at all, would have to be impossibly large. It would also have no connection to how doctors actually work.
The biggest skeptics were the FDA's own staff, who even before the vote had suggested the device might do more harm than good if doctors treated instances where MelaFind didn't render a verdict as the equivalent of an "all-clear." Why doctors would do this is hard to fathom. In the study, so many of the "nonevaluable" lesions turned out be melanomas precisely because doctors were focusing MelaFind on lesions they considered highly suspicious even though the lesions were too big or oddly situated to fit the device's design criteria. Says Dr. Gulfo: "The FDA seems to be assuming that doctors, some of the most highly trained people in our society, are not competent to operate this device that dermatologists tell us has the potential to save many lives."
Though the agency itself will ultimately rule yea or nay, it clearly emerged from the meeting that doctors crave a device to aid in making the often difficult decision about whether a given lesion is worrisome. Dr. Gulfo explained the training users would receive. He explained the user log-on to prevent untrained use. He might have added that the CAT scan and MRI never would have been approved if inventors had to guarantee against incompetent use. The vital point was made by one of the panelists: "At the end of the day, MelaFind is going to allow some people to die; dermatologists are going to allow some people to die. I believe that MelaFind is going to help a few less people die and that's why I voted yes."
Of course, nobody at the FDA is ever fired for failing to approve a device. So grating has the agency's hyper-cautiousness become that, under prodding from university researchers and Congress, it recently rolled out a plan to allow speedier reviews very similar to the agreement struck with Mela Sciences. How this promise is supposed to now have any credibility is itself a bit of a medical mystery.
MelaFind heralds a wave of devices bringing artificial intelligence to bear on medical diagnosis. In the hands of users, learning will occur. Improvements will come quickly, as in other areas of information technology. Many lives will be saved, if the FDA will let them.
WSJ: Doc, hounded into suicide by FDA, vindicated
Reply #8 on:
December 26, 2012, 08:45:28 AM »
A Doctor's Posthumous Vindication
Peter Gleason spoke his mind about a drug's benefits—then saw his career ruined by the FDA and federal prosecutors..
By HARVEY SILVERGLATE
Peter Gleason was a psychiatrist who devoted much of his professional life to caring for what government officials call "underserved populations." He would have been thrilled to learn that on Dec. 3 in New York, a three-judge panel of the U.S. Court of Appeals for the Second Circuit issued a ringing opinion that vindicated the conduct for which he was indicted and arrested in 2006.
Unfortunately, Gleason did not live to see this welcome reversal of the federal government's crusade against him and the promotion of Xyrem—a drug widely used by physicians, including Gleason, to treat a number of medical conditions beyond what the federal Food and Drug Administration approved it for. Hounded for years, he saw his career and finances ruined by the relentless war waged against him by FDA bureaucrats and Justice Department prosecutors. Gleason committed suicide on Feb. 7, 2011.
The doctor's troubles stemmed from lectures he gave attesting to the efficacy of Xyrem, a pharmaceutical originally developed for use in narcolepsy but found by physicians to be effective against a number of conditions, including fibromyalgia and chronic fatigue syndrome. The FDA had not given formal approval for these so-called "off-label" uses since the manufacturer had not submitted an application covering those ailments.
Obtaining FDA approval for a new drug is time-consuming and expensive. Once a drug is approved for a certain use (which its FDA-approved "label" describes), physicians often discover, through use of the drug as well as through further research and field experience, other conditions for which the drug is a safe and effective remedy. Manufacturers rarely go through the FDA approval process for such additional uses of already-approved drugs due to the expense. FDA regulations forbid them to promote these "off-label" uses.
Yet such uses are widely practiced by experienced physicians. They know, for instance, that Neurontin, approved to treat seizures, can also relieve neuropathic, or nerve, pain. Avastin, approved to limit new blood-vessel growth in tumors, ameliorates age-related muscular degeneration. Aspirin is widely deemed a miracle drug because of its uses beyond pain relief, largely discovered by trial and error.
Unlike manufacturers, physicians are not restricted by federal law from prescribing an FDA-approved drug for an off-label condition. They are perfectly free to communicate the results of their experience to fellow physicians, or to publish in medical journals. Such communications have long been recognized to be protected by the physicians' professional prerogatives and free-speech rights.
So how was it that Gleason was indicted on a conspiracy charge of communicating to his fellow physicians that he found Xyrem effective for off-label medical conditions such as chronic pain and bipolar disorder? Gleason, it turns out, often revealed his experiences with Xyrem to audiences of physicians during paid appearances at events sponsored by its maker, Orphan Medical—a common practice within the medical community. The prosecutors' convoluted legal theory was that even if Gleason himself was free to recommend Xyrem, he had lost his First Amendment right to communicate his medical knowledge because he had become an agent of sorts for the manufacturer and "conspired" with employees of the company, who had to stick to promoting only FDA-approved uses.
No wonder Gleason was shocked when he found himself surrounded and handcuffed by six federal agents who were waiting for him at a train station on New York's Long Island on March 6, 2006. When prosecutors could not convince Gleason to cooperate against the drug manufacturer—he did not feel that either he or Orphan Medical had violated the law—they indicted him, triggering a downward spiral that wreaked havoc on his medical practice.
Gleason was not a wealthy man, but whatever assets he had accumulated during his working life were placed in limbo when the feds included in the indictment a "criminal forfeiture allegation." This sought to force him to turn over to the government "any property, real and personal, that constitutes or is derived, directly or indirectly, from gross proceeds traceable to the commission of offenses." Virtually all of Gleason's income and assets were derived from his medical practice. Thus prevented from hiring private counsel of his choice, he required free legal representation from the Federal Defenders Service, tasked with representing indigent defendants.
The ordeal of fighting a federal indictment, a daunting process even for the wealthy, exhausted Gleason, with whom I corresponded when I included his case in a book I was writing about how federal bureaucrats and prosecutors go after innocent defendants for innocuous behavior. He grew increasingly dispirited and finally decided to accept an offer that he felt he could not refuse. He pleaded guilty to a misdemeanor alleging his conspiracy with Orphan Medical and was sentenced to one year of probation and a $25 fine.
But Gleason's career was ruined and his pride decimated. He had difficulty holding a hospital or clinic job, and his medical license was placed into question. He was despondent the last time I spoke with him, and he subsequently took his life by hanging himself.
Just under two years later, Gleason's posthumous vindication was achieved by his co-defendant, Alfred Caronia, a sales representative for Xyrem's manufacturer, Orphan Medical (later acquired by Jazz Pharmaceuticals JAZZ +0.44%), who had refused to make a deal with the feds. With the aid of aggressive legal counsel and the "friend-of-the-court" backing of two public-interest organizations, Mr. Caronia won the point that Gleason had many times argued to anyone who would listen: The First Amendment protects the right of physicians, drug manufacturers, sales representatives and anyone else who wishes to convey truthful, factual information about the beneficial uses of drugs in the relief of illness and pain.
What the appeals court affirmed in ruling for the defendants on Dec. 3 seems so obvious now. But it's too late for Peter Gleason. And too late for the feds to apologize, if they were so inclined.
Mr. Silverglate, a Boston lawyer, is the author of "Three Felonies a Day: How the Feds Target the Innocent" (Encounter Books, 2009).
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