Charnel House
This essay was originally published by The Radical Capitalist Inserts on December 28, 2002
The state must not put the innocent to death. Declarations like "It is better to let ten killers go free than to execute one falsely convicted" attempt to demonstrate the value of this imperative.
But our government condemns the innocent to death everyday, and covers itself with excuses that barely qualify as coherent phrases. Its executioner is the Food and Drug Administration, and its weapons are prohibition and the sugar pill.
Perhaps, you think, this is not the best time to call attention to the matter. The nation's collective attention span is occupied at present with the impending attempt to topple the regime of Saddam Hussein. That same dictator is, by credible accounts, seeking means to douse us with nerve gas and smallpox, and perhaps even destroy some of us in a nuclear blast. The North Koreans are threatening us with unspecified catastrophe, after letting the world know that it has nuclear weapons and the missiles with which to deliver them. Why should we distract ourselves to hear the charge that the perpetrators of systematic homicide walk our streets unrecognized in the daylight? That they constitute a cadre of federal agents entrusted with regulating our efforts to survive disease? That they are not wild-eyed suicides with bombs strapped to their backs, but deliberate men and women manicured, coiffed, and flashing badges?
I submit that if we have time to entertain the late theory that voting for affirmative action quotas exonerates a man for a history of sheet-wearing and cross-burning, we have more than enough time to consider what moves the creatures inhabiting the US government's most macabre agency. Consider these cases in point:
* Several researchers have found Ecteinasicidin-743 (ET-743) safe and effective for the treatment of soft-tissue sarcoma (STS). Researchers at the Fox Chase Cancer Center in Philadelphia believe that the drug may also be effective in the treatment of advanced breast cancer.
Spanish pharmaceutical PharmaMar developed ET-743 and has licensed it for sale outside Europe to a subsidiary of Johnson & Johnson.1 In June of 2001, the FDA made public a letter it had earlier sent to PharmaMar USA, citing the pharmaceutical for making unauthorized claims for ET-743, and instructing it to withdraw the brochure in which the claims were made. The letter, written by a gentleman with the title of Regulatory Review Officer, states:
He then proceeds to list the violations; i.e., excerpts from results of studies showing ET-743 safe and effective. According to the Regulatory Review Officer, it is a federal offense for a pharmaceutical to convey this information to cancer specialists.
There is the chance you will think that the abstracts and claims published in the PharmaMar brochure were concocted by a PharmaMar press agent, and made up of the sort of anecdotal ejaculations solicited by media companies on behalf of extra-strength aspirin manufacturers. - And that PharmaMar was trying to palm these representations off on unsuspecting oncologists while real scientists were as yet unprepared to draw conclusions. But that is not the case. The "Demetri et al" to which the Regulatory Review Officer refers is, according to his own cite:
George D. Demetri and Judith Manola of the Dana-Farber Cancer Institute
David Harmon of Massachusetts General Hospital
Robert G. Maid of Memorial Sloan-Kettering Cancer Center
Several researchers from PharmaMar
The Regulatory Review Officer does not say that he has a problem with the stature of the scientists, research, or institutions involved. He does not express concern that PharmaMar might be trying to pass off its own conclusions as the conclusions of the scientists listed above. He does not contend that the results published by these doctors are at variance with the conclusions drawn by his own colleagues as a result of their existing research. PharmaMar's offense is that it cites any results at all in favor of its product from sources not yet corroborated by federal bureaucrats.
The FDA has not fully tested ET-743. Thus, as far as the public - including oncologists - must be concerned, it has not been tested. For a pharmaceutical to say otherwise, even when it is the truth, is to violate federal regulations.
But where, you no doubt want to know, is the death? Where is the charnel house? PharmaMar might have a First Amendment case, given a sane judge, but whom is the FDA actually killing?
Consider the timeline. When the Regulatory Review Officer wrote the above letter, George Demetri had already published, in collaboration with several other investigators, various studies showing the safety and efficacy of ET-743,3 but the FDA was not and is not to this day ready to approve the drug. Earlier this year, the American Cancer Society stated that "During 2002, 3,900 Americans (2,000 males and 1,900 females) are expected to die of soft tissue sarcomas."4 Thus, while the Regulatory Review Officer was worried that PharmaMar might tell oncologists that researchers at Dana Farber and Sloan-Kettering had found ET-743 safe and effective in the treatment of STS, the patients of those oncologists were dying from the disease at a rate of more than 10 souls per day.
Pretty good output for a slaughterhouse.
If you were unlucky enough to be a victim of STS, and you were looking for a safe and effective treatment, do you think you would be more likely to trust the tests run by the doctors at Sloan-Kettering and Dana Farber, or the tests run by the colleagues of the Regulatory Review Officer?
But there is no need to resort to hypotheticals on this head. Edie Bacon, an FDA victim afflicted with STS, told her story in a guest editorial for the Wall Street Journal on November 29. Says Bacon:
Implied in the first paragraph quoted above is a bizarre methodology. If Mrs. Bacon is repeating what she has been told by the colleagues of the Regulatory Review Officer (and I have no reason to doubt that she is), the FDA fears that results of tests conducted on a sample of the total population of STS patients will be invalidated if someone outside the sample exhibits unexpected symptoms.
As I said, this is a bizarre methodology. If and when ET-743 is approved by the FDA, it will be tested again and again over the years by researchers attempting to account for hitherto-unexpected side-effects and benefits; researchers hired by hospitals, foundations, and pharmaceuticals. Each of these trials will serve to refine, confirm, or refute observations made by the clinicians in San Antonio, each trial will conclude in hypotheses that will themselves be open to later refinement, confirmation, and refutation, and not one of them will require that the rest of the world stop taking ET-743 for fear of "tainting" the research.
Scientific research is an exercise in open-ended induction. That is, it is a process of arriving at generalizations about all entities of a certain kind based upon observations of only some of those entities. This means that these generalizations must always remain open to revision as more entities of the given kind are observed. This is not an invitation to subjectivity: at any point in time, the best generalizations will be based upon the most reliable observations, and abstracted according to a process of reason.
When a researcher abstracts general principles about STS patients based on a sample of those patients, he or she does so with the understanding that the abstractions may be refined, amended, or invalidated by studies that come later, and that at no time can any researcher rationally claim that the final knowledge has been acquired, that no more research need be done.
Thus, the FDA's fear that results outside the test population might spoil the results of their experiments is a fear alien to the process of scientific induction.. What, then, gives it rise? I submit that the FDA is here motivated solely by its political mandate; namely, to provide certain guarantees at a fixed point in time regarding the safety and efficacy of medical treatments. I further submit that, as a consequence, the FDA cannot afford to risk piercing the illusion that its San Antonio sample is a perfect representation of all STS victims. - And nothing would pierce that illusion faster than an unsampled STS patient with symptoms not experienced in the test group.
If the colleagues of the Regulatory Review Officer were to state from the outset that their sampling methodology comes with an unavoidable error rate, that they are fully aware that members of the unsampled population may not be represented in the sample and that they may therefore have reactions not found in tests conducted on the sample, that their observations are open to revision and refutation by the next team of doctors that takes up the research, they would be admitting that their political mandate is incompatible with induction per se and good only to perpetuate the illusion that reality is whatever the man with the badge says it is. - These bold men and women would be racked in an open session of congress and lectured by the resident technocrats for the dereliction of their duty to provide the public with assurances of safety. - But they would be right.
*BPI (bactericidal/permeability-increasing protein) is an experimental drug for the treatment of meningococcal disease. Symptoms of meningococcal disease mimic those of the flu early on, but hours after the onset of first symptoms the victim develops purple splotches and blackened fingertips as limbs begin to develop gangrene. Within six hours the victim can be dead. Those who survive often do so only after limbs have been amputated.
According to Brett Giroir, of the Children's Medical Center in Dallas:
In a trial for FDA approval, BPI reduced amputations by 65 percent and increased survival by 25 percent. But the FDA did not find these figures statistically significant, so the application for the drug's approval was rejected. Why did BPI save only one out of four patients receiving it? Again, according to Giroir:
The implication: no effective treatment for meningococcal disease can at present be approved by the state, because the disease does not meet the FDA's standard schedule.
In the world where failure and success matter to business and reputation - in any laboratory where science takes priority, the form of an experiment is structured to fit the function of the subject under study. You do not demand that people take on the characteristics of rats because you are used to testing rats, and you do not recycle the methodology for researching arthritis as a methodology for studying a burst appendix.
But the unaccountable colleagues of the Regulatory Review Officer have no business at stake. They have the statutory power to compel, so their reputations are beside the point. Their answer to the problem of induction is more straightforward than Dr. Giroir's. They let you die.
*ImClone, Inc., is perhaps best known for accusations that insiders sold their stock in the firm when they learned that the FDA had refused to approve its colorectal cancer drug, Erbitux, but before this information became available to the general public.
Why did the FDA reject Erbitux?
A look at ImClone's article8 on Erbitux indicates that the manufacturer sees the drug as part of a compound treatment including other therapies (such as radiation or chemotherapy). The FDA, on the other hand, is interested in acquiring, by an arbitrary deadline, out-of-context information on Erbitux. It is as if you saw a man drowning and prepared to throw him a buoy attached to the end of a long rope. Before you can, a regulator runs up and says: "Don't throw him the rope and the buoy! Just throw him the buoy!" You know the buoy is no good without the rope to pull the drowning man to shore. The regulator only knows it will probably be a long time before he gets another opportunity to see how long a buoy will stay afloat under a man who really believes he is struggling for his life.
Why not let researchers determine - if they're interested - the acontextual behavior of buoys after the drowning man has been saved? Why not continue tests on Erbitux after colorectal cancer patients are permitted to use it in combination with irinotecan? According to the New York Times:
That is, the FDA needs to threaten colorectal cancer patients with earlier death so that they will be "encouraged" to volunteer for lab-rat service. The agency is probably right. If you were a terminal cancer patient with the choice of getting Erbitux and knowing it was Erbitux, or of getting "Erbitux" and knowing there was a significant chance that it was really a placebo, which would you choose?
A placebo trial conducted on the terminally ill is a form of torture. How else do you describe a condition attended by extreme physical pain and compounded by the knowledge that the treatment you are counting on to save or extend your life may in fact be nothing more than sugar pills? Perhaps you believe that said patients are not thinking of themselves at this point, but of what the colleagues of the Regulatory Review Officer no doubt consider the greater good. Perhaps you live in a bog on the moon. Perhaps you believe that placebo tests are necessary to determine efficacy. They are not. Placebo tests exist solely to control for the psychobiological effects on the subject of the subject's believing he is receiving treatment. - And when the process is not lethal, and the test subjects are not coerced, it is reasonable to expect scientists to seek this level of precision. But I submit that if allowing patients to die is the only way you can know that a given treatment shrinks tumors 2.5 centimeters rather than somewhere in the range of 1 to 3 centimeters, you learn to live with the range.
That patients should not be coerced into taking part in clinical trials is also the view of the authors of the Nuremberg Code, written in reaction to the atrocities committed, in the name of medical research, by the Nazi Third Reich. The Nazi doctors knew, for instance, that pilots who ditched in the North Sea could survive for approximately two hours. But they wanted a more precise measure, and got one by throwing concentration camp inmates into tanks of freezing water and starting a stopwatch.
The Nuremberg Code states, in part:
I do not know who has provided the New York Times with the casual assertion that the FDA uses legal prohibition to prevent terminal cancer patients from acquiring treatment, and that it does so for the purpose of ensuring that enough of them will "volunteer" to gamble their lives in placebo trials. But if the FDA did not provide this information itself, and if it is scandalized by the implication that flouting the Nuremberg Code is its standard operating procedure, its outrage has not been heard in public.
One rationalization you will hear from the FDA's apologists is that the agency is "protecting the public safety." It is a mantra.
What is this public, if not an abstraction subsuming all individuals in a society, including the men, women, and children the FDA sentences regularly to early and agonizing deaths? It is a totem. A myth. A collectivist hangover. If the public safety - whatever it is - requires the use of force to prevent doctors from saving or extending the lives of the dying, then "public safety" is a public menace, and to hell with it.
Only the human mind is capable of making value judgments, and this faculty isn't enhanced when the individual possessing it takes a government job. The actions necessary to saving the lives of the terminally ill have to be chosen by someone, and that person is, properly, the individual whose life or future is at risk for acting or not acting. It is the government's job to see to it that no one interferes with the exercise of this faculty: it is not the government's job to stop you if the method you choose to save your life does not meet the state's unaccountable specifications.
A common objection to this view is that, without a laboratory in your basement, you are not qualified to make judgments about chemicals, cures, and DNA. In reality, you rely every day on specialists for your comfort, health, and security precisely because they have knowledge that you do not. And if you are prudent you rely on the expertise of intermediates to bring that specialized information within reach of your understanding. You trust lawyers to speak for you to a court, because you lack the education and training to do so directly. If you are building a house, you trust your general contractor to manage subcontractors because you lack the expertise to manage them yourself. You trust doctors and panels of doctors to prescribe treatments for you, because you are not a doctor and cannot treat yourself. Where does your judgment come in? You are the one who judges the lawyer, the general contractor, and the doctor. You judge them by record and reputation and by the consonance of their representations of fact with what you already know and what you observe firsthand.
The notion that we would all have to be research specialists to have confidence in a cancer therapy is a canard, potentially lethal. It is a rationalization so thin that believing it is a burden on the honest imagination. If the general principle were true, we would all be living in hand-built shacks sewing our own clothes with needles we forged ourselves.
Another objection contends that doing away with the state's power to prohibit medications is too drastic. That perhaps a new, streamlined government agency should replace or complement the FDA, but that we cannot leave standards to a market "free-for-all."
The market cannot guarantee the absolute safety or efficacy of anything. Neither can the state. But it is the "free-for-all" nature of the market that keeps standards from becoming the monopoly of a single institution, and consequently makes one player accountable not only for the safety and efficacy of its drugs, but for their comparative safety and efficacy. Private panels, accountable for their reputations among consumers, doctors, and businessmen, risk losing customers to their rivals when they offer prejudiced advice based on obscure, self-aggrandizing, or obsolete standards. To gain dominance in the market, standards must be based on the current state-of-the art by participants who have an interest in being able to measure any given product or service against real alternatives. The government has no such interest, so cancer patients forced to accept its standards suffer a fate far worse than the fate suffered by investors who bought stocks while trusting government accounting standards. When standards are a matter of state decree, the given instance of a real product - like a treatment for cancer - can be measured against a "standard" that is based on a non-existent ideal. The result: your child is dying of meningococcal disease because the FDA believes that BPI's 25 percent cure rate is statistically insignificant.. Insignificant, you ask, compared with what? But the FDA does not have to provide an alternative, because it is not part of the market "free-for-all." It holds your child's life in its hands because it is protected by statute, and can base its standards on imaginary, perfect alternatives.
The FDA's political constituent is not the citizen in search of high standards, but the constitutional mystic in search of authority. The FDA provides this constituent with the illusion, described earlier, that knowledge about diseases and cures is static; that the "guarantees" the state makes for a medication or therapy are absolute and therefore not open to revision. This constituent is then scandalized when a long-approved therapy is discovered to have limitations not observed by the original investigators. This, for him, is not evidence of the open-ended nature of induction, but of slipshod work and, perhaps, of bribed public servants. For him, any explanation whatever of contextual knowledge refined by new data sounds like the legalisms of some slacker trying to weasel out of a promise. - And if the state cannot make researchers keep their promises and get it right the first time, who can?
Accepting that the individual must use his mind in order to survive, and that free governments are constituted to protect that use, not pre-empt it, means getting the government out of the medical standards business. Its influence there is not calculated to improve quality or performance, but to provide unction for the superstitious.
The resulting charnel house is such a horror that most Americans will not believe their government capable of the atrocity. - And they may not become aware unless they become terminally ill themselves, with an effective drug put out of their reach by the colleagues of the Regulatory Review Officer. Then they will know what it is like to be the confidant of a lethal outrage, while outside the clinic the world still turns for the unsuspecting, and nobody gives a damn.
—Dan Roentsch
1October 22, 2002. "Fox Chase Cancer Center Studies Breast Cancer Drug Made from 'Sea Squirts'". Philadelphia: the Fox Chase Cancer Center. Available from World Wide Web: (www.fccc.edu/news/2002/Sea-Squirt-10-21-2002.html)."Breast cancer, when caught early, often can be successfully treated, but fewer treatment options exist for women whose cancer has spread," said Lori J. Goldstein, M.D., director of the breast evaluation center at Fox Chase and principal investigator for the latest ET-743 study. "Since the beginning of time, we have turned to nature to find medicinal agents. This time, we're looking to the sea with hopes that the sea squirt drug can help us treat advanced breast cancer."
2Rumble, Warren F. letter of regulatory review officer to PharmaMar USA Vice President Flaircloth, Glynn T., 25 June 2001 [date released by FDA]. Available from World Wide Web (http://www.pharmcast.com/WarningLetters/Yr2001/June2001/PharmaMar0601.htm)
3Several of these papers are available from the World Wide Web. See for example http://www.mesotheliomaweb.org/marinecure.htm, and PharmaMar's European (hence beyond the reach of the Regulatory Review Officer) Website: http://www.pharmamar.es/en/prosci/facts_001.cfm
4American Cancer Society. "What Are The Key Statistics For Sarcoma?" Available on World Wide Web (http://www.cancer.org).
5Susan Fitzgerald, "Braving disease that can kill or maim in hours," Knight Ridder Newspapers. Available from World Wide Web (http://www.grandforks.com/mld/grandforks/news/nation/4447551.htm).
6"Killer Disease on Campus," Narr. Will Lyman. NOVA. PBS. 3 September 2002. Transcript available from World Wide Web (http://www.pbs.org/wgbh/nova/transcripts/2909_meningit.html).
7Adam Feuerstein, "ImClone Could Get Erbitux Approval Within a Year," TheStreet.com. (http://www.thestreet.com/tech/adamfeuersteing/10010676.html).
9Andrew Pollack, "Partners Promise New Tests of Cancer Drug," The New York Times, 4 October 2002.[Part of the Times' premium archive. Requires purchase.]
10The Nuremberg Code is available on the World Wide Web from the National Institutes of Health, Office of Human Subjects Research. (http://ohsr.od.nih.gov/nuremberg.php3)
The state must not put the innocent to death. Declarations like "It is better to let ten killers go free than to execute one falsely convicted" attempt to demonstrate the value of this imperative.
But our government condemns the innocent to death everyday, and covers itself with excuses that barely qualify as coherent phrases. Its executioner is the Food and Drug Administration, and its weapons are prohibition and the sugar pill.
Perhaps, you think, this is not the best time to call attention to the matter. The nation's collective attention span is occupied at present with the impending attempt to topple the regime of Saddam Hussein. That same dictator is, by credible accounts, seeking means to douse us with nerve gas and smallpox, and perhaps even destroy some of us in a nuclear blast. The North Koreans are threatening us with unspecified catastrophe, after letting the world know that it has nuclear weapons and the missiles with which to deliver them. Why should we distract ourselves to hear the charge that the perpetrators of systematic homicide walk our streets unrecognized in the daylight? That they constitute a cadre of federal agents entrusted with regulating our efforts to survive disease? That they are not wild-eyed suicides with bombs strapped to their backs, but deliberate men and women manicured, coiffed, and flashing badges?
I submit that if we have time to entertain the late theory that voting for affirmative action quotas exonerates a man for a history of sheet-wearing and cross-burning, we have more than enough time to consider what moves the creatures inhabiting the US government's most macabre agency. Consider these cases in point:
* Several researchers have found Ecteinasicidin-743 (ET-743) safe and effective for the treatment of soft-tissue sarcoma (STS). Researchers at the Fox Chase Cancer Center in Philadelphia believe that the drug may also be effective in the treatment of advanced breast cancer.
Spanish pharmaceutical PharmaMar developed ET-743 and has licensed it for sale outside Europe to a subsidiary of Johnson & Johnson.1 In June of 2001, the FDA made public a letter it had earlier sent to PharmaMar USA, citing the pharmaceutical for making unauthorized claims for ET-743, and instructing it to withdraw the brochure in which the claims were made. The letter, written by a gentleman with the title of Regulatory Review Officer, states:
The Division of Drug Marketing, Advertising, and Communications (DDMAC) has identified promotional materials and activities for Ecteinasicidin-743, an investigational new drug, that are in violation of the Federal Food, Drug, and Cosmetic Act (act) and its implementing regulations. Specifically, PharmaMar distributed a brochure in the commercial exhibit hall at the 37th American Society of Clinical Oncology (ASCO) Annual meeting held in San Francisco, California, May 12-15, 2001, that made conclusions about safety and efficacy for the investigational new drug. ...
Sponsors may not represent in a promotional context that an investigational new drug is safe or effective for the uses that are under investigation (see 21 CFR 312.7(a)). Your brochure titled, 'The PharmaMar Oncology Pipeline: Meeting Presentations,' however, includes many abstracts that present claims and representations concerning the safety or efficacy of Ecteinasicidin-743, an investigational new drug.
For example, in the abstract by Demetri et al ... 2
He then proceeds to list the violations; i.e., excerpts from results of studies showing ET-743 safe and effective. According to the Regulatory Review Officer, it is a federal offense for a pharmaceutical to convey this information to cancer specialists.
There is the chance you will think that the abstracts and claims published in the PharmaMar brochure were concocted by a PharmaMar press agent, and made up of the sort of anecdotal ejaculations solicited by media companies on behalf of extra-strength aspirin manufacturers. - And that PharmaMar was trying to palm these representations off on unsuspecting oncologists while real scientists were as yet unprepared to draw conclusions. But that is not the case. The "Demetri et al" to which the Regulatory Review Officer refers is, according to his own cite:
George D. Demetri and Judith Manola of the Dana-Farber Cancer Institute
David Harmon of Massachusetts General Hospital
Robert G. Maid of Memorial Sloan-Kettering Cancer Center
Several researchers from PharmaMar
The Regulatory Review Officer does not say that he has a problem with the stature of the scientists, research, or institutions involved. He does not express concern that PharmaMar might be trying to pass off its own conclusions as the conclusions of the scientists listed above. He does not contend that the results published by these doctors are at variance with the conclusions drawn by his own colleagues as a result of their existing research. PharmaMar's offense is that it cites any results at all in favor of its product from sources not yet corroborated by federal bureaucrats.
The FDA has not fully tested ET-743. Thus, as far as the public - including oncologists - must be concerned, it has not been tested. For a pharmaceutical to say otherwise, even when it is the truth, is to violate federal regulations.
But where, you no doubt want to know, is the death? Where is the charnel house? PharmaMar might have a First Amendment case, given a sane judge, but whom is the FDA actually killing?
Consider the timeline. When the Regulatory Review Officer wrote the above letter, George Demetri had already published, in collaboration with several other investigators, various studies showing the safety and efficacy of ET-743,3 but the FDA was not and is not to this day ready to approve the drug. Earlier this year, the American Cancer Society stated that "During 2002, 3,900 Americans (2,000 males and 1,900 females) are expected to die of soft tissue sarcomas."4 Thus, while the Regulatory Review Officer was worried that PharmaMar might tell oncologists that researchers at Dana Farber and Sloan-Kettering had found ET-743 safe and effective in the treatment of STS, the patients of those oncologists were dying from the disease at a rate of more than 10 souls per day.
Pretty good output for a slaughterhouse.
If you were unlucky enough to be a victim of STS, and you were looking for a safe and effective treatment, do you think you would be more likely to trust the tests run by the doctors at Sloan-Kettering and Dana Farber, or the tests run by the colleagues of the Regulatory Review Officer?
But there is no need to resort to hypotheticals on this head. Edie Bacon, an FDA victim afflicted with STS, told her story in a guest editorial for the Wall Street Journal on November 29. Says Bacon:
ET 743 is now being tested in San Antonio. Any outside use of the drug that cannot be monitored directly by the doctors in charge of the test could 'taint' the whole test, if the patient were to experience an unpredicted symptom. Even if the symptom were minor and seemingly unrelated, like feeling dizzy in an overheated car, questions could be raised about the drug, jeopardizing its approval. The FDA could require more tests, costing Johnson & Johnson millions more in testing costs and delays and hurting its reputation with the FDA. ...
If you're me, you wonder what the FDA is thinking. I'm dying here; I'm a citizen and a taxpayer. Why must Johnson & Johnson be paralyzed by the prospect of getting in trouble with the government if it gives its drug to dying people? The drug has already made it through several phase one trials and shown itself to be safe.
Implied in the first paragraph quoted above is a bizarre methodology. If Mrs. Bacon is repeating what she has been told by the colleagues of the Regulatory Review Officer (and I have no reason to doubt that she is), the FDA fears that results of tests conducted on a sample of the total population of STS patients will be invalidated if someone outside the sample exhibits unexpected symptoms.
As I said, this is a bizarre methodology. If and when ET-743 is approved by the FDA, it will be tested again and again over the years by researchers attempting to account for hitherto-unexpected side-effects and benefits; researchers hired by hospitals, foundations, and pharmaceuticals. Each of these trials will serve to refine, confirm, or refute observations made by the clinicians in San Antonio, each trial will conclude in hypotheses that will themselves be open to later refinement, confirmation, and refutation, and not one of them will require that the rest of the world stop taking ET-743 for fear of "tainting" the research.
Scientific research is an exercise in open-ended induction. That is, it is a process of arriving at generalizations about all entities of a certain kind based upon observations of only some of those entities. This means that these generalizations must always remain open to revision as more entities of the given kind are observed. This is not an invitation to subjectivity: at any point in time, the best generalizations will be based upon the most reliable observations, and abstracted according to a process of reason.
When a researcher abstracts general principles about STS patients based on a sample of those patients, he or she does so with the understanding that the abstractions may be refined, amended, or invalidated by studies that come later, and that at no time can any researcher rationally claim that the final knowledge has been acquired, that no more research need be done.
Thus, the FDA's fear that results outside the test population might spoil the results of their experiments is a fear alien to the process of scientific induction.. What, then, gives it rise? I submit that the FDA is here motivated solely by its political mandate; namely, to provide certain guarantees at a fixed point in time regarding the safety and efficacy of medical treatments. I further submit that, as a consequence, the FDA cannot afford to risk piercing the illusion that its San Antonio sample is a perfect representation of all STS victims. - And nothing would pierce that illusion faster than an unsampled STS patient with symptoms not experienced in the test group.
If the colleagues of the Regulatory Review Officer were to state from the outset that their sampling methodology comes with an unavoidable error rate, that they are fully aware that members of the unsampled population may not be represented in the sample and that they may therefore have reactions not found in tests conducted on the sample, that their observations are open to revision and refutation by the next team of doctors that takes up the research, they would be admitting that their political mandate is incompatible with induction per se and good only to perpetuate the illusion that reality is whatever the man with the badge says it is. - These bold men and women would be racked in an open session of congress and lectured by the resident technocrats for the dereliction of their duty to provide the public with assurances of safety. - But they would be right.
*BPI (bactericidal/permeability-increasing protein) is an experimental drug for the treatment of meningococcal disease. Symptoms of meningococcal disease mimic those of the flu early on, but hours after the onset of first symptoms the victim develops purple splotches and blackened fingertips as limbs begin to develop gangrene. Within six hours the victim can be dead. Those who survive often do so only after limbs have been amputated.
Of the 3,000 people who get the bacterial infection each year in the United States, 10 to 13 percent die. ...
Among the survivors, 10 to 15 percent end up with some life-altering disability - brain damage, deafness, a loss of toes, fingers, arms or legs.5
According to Brett Giroir, of the Children's Medical Center in Dallas:
[BPI] is not some artificial substance produced somewhere in someone's laboratory. This is an exact copy of a normal, natural protein found in your white blood cells, your infection fighting cells. Not only does BPI kill bacteria but it completely binds and neutralizes endotoxin, the primary toxin that we think is the bad player. ...
We gave it to a girl, a nine-year-old girl from east Texas, who actually had to have CPR and be revived twice before she actually came to our hospital. And she had a magnificent, wonderful outcome after treatment with BPI and all the care we gave her.6
In a trial for FDA approval, BPI reduced amputations by 65 percent and increased survival by 25 percent. But the FDA did not find these figures statistically significant, so the application for the drug's approval was rejected. Why did BPI save only one out of four patients receiving it? Again, according to Giroir:
It's easy to do a trial if you have a million people with heart disease on any given day. But it's very difficult to do a trial in a rapidly progressive disease like meningococcal disease, that by the time you get the patients many of them are dead, in a disease that's so rare, and in a disease where, I think, the rules are different. ...
So if one of my children came into the hospital today with meningococcal sepsis, they couldn't get BPI, even though I know it works. There's no way to supply it.
The implication: no effective treatment for meningococcal disease can at present be approved by the state, because the disease does not meet the FDA's standard schedule.
In the world where failure and success matter to business and reputation - in any laboratory where science takes priority, the form of an experiment is structured to fit the function of the subject under study. You do not demand that people take on the characteristics of rats because you are used to testing rats, and you do not recycle the methodology for researching arthritis as a methodology for studying a burst appendix.
But the unaccountable colleagues of the Regulatory Review Officer have no business at stake. They have the statutory power to compel, so their reputations are beside the point. Their answer to the problem of induction is more straightforward than Dr. Giroir's. They let you die.
*ImClone, Inc., is perhaps best known for accusations that insiders sold their stock in the firm when they learned that the FDA had refused to approve its colorectal cancer drug, Erbitux, but before this information became available to the general public.
Why did the FDA reject Erbitux?
The trial conducted by ImClone started with colon cancer patients who had previously failed treatment with [the chemotherapy drug] irinotecan. It then gave them a combination of Erbitux and irinotecan. This test yielded a 22.5% response rate, according to ImClone.
But FDA officials said ImClone didn't provide proof that these patients had actually failed previous treatments. Therefore, the results were meaningless because the agency could not determine which drug - Erbitux or irinotecan - was actually responsible for the positive results.7
A look at ImClone's article8 on Erbitux indicates that the manufacturer sees the drug as part of a compound treatment including other therapies (such as radiation or chemotherapy). The FDA, on the other hand, is interested in acquiring, by an arbitrary deadline, out-of-context information on Erbitux. It is as if you saw a man drowning and prepared to throw him a buoy attached to the end of a long rope. Before you can, a regulator runs up and says: "Don't throw him the rope and the buoy! Just throw him the buoy!" You know the buoy is no good without the rope to pull the drowning man to shore. The regulator only knows it will probably be a long time before he gets another opportunity to see how long a buoy will stay afloat under a man who really believes he is struggling for his life.
Why not let researchers determine - if they're interested - the acontextual behavior of buoys after the drowning man has been saved? Why not continue tests on Erbitux after colorectal cancer patients are permitted to use it in combination with irinotecan? According to the New York Times:
Making the drug too widely available could discourage patients from enrolling in the trials needed to obtain approval for the drug.9
That is, the FDA needs to threaten colorectal cancer patients with earlier death so that they will be "encouraged" to volunteer for lab-rat service. The agency is probably right. If you were a terminal cancer patient with the choice of getting Erbitux and knowing it was Erbitux, or of getting "Erbitux" and knowing there was a significant chance that it was really a placebo, which would you choose?
A placebo trial conducted on the terminally ill is a form of torture. How else do you describe a condition attended by extreme physical pain and compounded by the knowledge that the treatment you are counting on to save or extend your life may in fact be nothing more than sugar pills? Perhaps you believe that said patients are not thinking of themselves at this point, but of what the colleagues of the Regulatory Review Officer no doubt consider the greater good. Perhaps you live in a bog on the moon. Perhaps you believe that placebo tests are necessary to determine efficacy. They are not. Placebo tests exist solely to control for the psychobiological effects on the subject of the subject's believing he is receiving treatment. - And when the process is not lethal, and the test subjects are not coerced, it is reasonable to expect scientists to seek this level of precision. But I submit that if allowing patients to die is the only way you can know that a given treatment shrinks tumors 2.5 centimeters rather than somewhere in the range of 1 to 3 centimeters, you learn to live with the range.
That patients should not be coerced into taking part in clinical trials is also the view of the authors of the Nuremberg Code, written in reaction to the atrocities committed, in the name of medical research, by the Nazi Third Reich. The Nazi doctors knew, for instance, that pilots who ditched in the North Sea could survive for approximately two hours. But they wanted a more precise measure, and got one by throwing concentration camp inmates into tanks of freezing water and starting a stopwatch.
The Nuremberg Code states, in part:
The voluntary consent of the human subject is absolutely essential. This means that the person involved should have legal capacity to give consent; should be so situated as to be able to exercise free power of choice, without the intervention of any element of force, fraud, deceit, duress, over-reaching, or other ulterior form of constraint or coercion.10
I do not know who has provided the New York Times with the casual assertion that the FDA uses legal prohibition to prevent terminal cancer patients from acquiring treatment, and that it does so for the purpose of ensuring that enough of them will "volunteer" to gamble their lives in placebo trials. But if the FDA did not provide this information itself, and if it is scandalized by the implication that flouting the Nuremberg Code is its standard operating procedure, its outrage has not been heard in public.
One rationalization you will hear from the FDA's apologists is that the agency is "protecting the public safety." It is a mantra.
What is this public, if not an abstraction subsuming all individuals in a society, including the men, women, and children the FDA sentences regularly to early and agonizing deaths? It is a totem. A myth. A collectivist hangover. If the public safety - whatever it is - requires the use of force to prevent doctors from saving or extending the lives of the dying, then "public safety" is a public menace, and to hell with it.
Only the human mind is capable of making value judgments, and this faculty isn't enhanced when the individual possessing it takes a government job. The actions necessary to saving the lives of the terminally ill have to be chosen by someone, and that person is, properly, the individual whose life or future is at risk for acting or not acting. It is the government's job to see to it that no one interferes with the exercise of this faculty: it is not the government's job to stop you if the method you choose to save your life does not meet the state's unaccountable specifications.
A common objection to this view is that, without a laboratory in your basement, you are not qualified to make judgments about chemicals, cures, and DNA. In reality, you rely every day on specialists for your comfort, health, and security precisely because they have knowledge that you do not. And if you are prudent you rely on the expertise of intermediates to bring that specialized information within reach of your understanding. You trust lawyers to speak for you to a court, because you lack the education and training to do so directly. If you are building a house, you trust your general contractor to manage subcontractors because you lack the expertise to manage them yourself. You trust doctors and panels of doctors to prescribe treatments for you, because you are not a doctor and cannot treat yourself. Where does your judgment come in? You are the one who judges the lawyer, the general contractor, and the doctor. You judge them by record and reputation and by the consonance of their representations of fact with what you already know and what you observe firsthand.
The notion that we would all have to be research specialists to have confidence in a cancer therapy is a canard, potentially lethal. It is a rationalization so thin that believing it is a burden on the honest imagination. If the general principle were true, we would all be living in hand-built shacks sewing our own clothes with needles we forged ourselves.
Another objection contends that doing away with the state's power to prohibit medications is too drastic. That perhaps a new, streamlined government agency should replace or complement the FDA, but that we cannot leave standards to a market "free-for-all."
The market cannot guarantee the absolute safety or efficacy of anything. Neither can the state. But it is the "free-for-all" nature of the market that keeps standards from becoming the monopoly of a single institution, and consequently makes one player accountable not only for the safety and efficacy of its drugs, but for their comparative safety and efficacy. Private panels, accountable for their reputations among consumers, doctors, and businessmen, risk losing customers to their rivals when they offer prejudiced advice based on obscure, self-aggrandizing, or obsolete standards. To gain dominance in the market, standards must be based on the current state-of-the art by participants who have an interest in being able to measure any given product or service against real alternatives. The government has no such interest, so cancer patients forced to accept its standards suffer a fate far worse than the fate suffered by investors who bought stocks while trusting government accounting standards. When standards are a matter of state decree, the given instance of a real product - like a treatment for cancer - can be measured against a "standard" that is based on a non-existent ideal. The result: your child is dying of meningococcal disease because the FDA believes that BPI's 25 percent cure rate is statistically insignificant.. Insignificant, you ask, compared with what? But the FDA does not have to provide an alternative, because it is not part of the market "free-for-all." It holds your child's life in its hands because it is protected by statute, and can base its standards on imaginary, perfect alternatives.
The FDA's political constituent is not the citizen in search of high standards, but the constitutional mystic in search of authority. The FDA provides this constituent with the illusion, described earlier, that knowledge about diseases and cures is static; that the "guarantees" the state makes for a medication or therapy are absolute and therefore not open to revision. This constituent is then scandalized when a long-approved therapy is discovered to have limitations not observed by the original investigators. This, for him, is not evidence of the open-ended nature of induction, but of slipshod work and, perhaps, of bribed public servants. For him, any explanation whatever of contextual knowledge refined by new data sounds like the legalisms of some slacker trying to weasel out of a promise. - And if the state cannot make researchers keep their promises and get it right the first time, who can?
Accepting that the individual must use his mind in order to survive, and that free governments are constituted to protect that use, not pre-empt it, means getting the government out of the medical standards business. Its influence there is not calculated to improve quality or performance, but to provide unction for the superstitious.
The resulting charnel house is such a horror that most Americans will not believe their government capable of the atrocity. - And they may not become aware unless they become terminally ill themselves, with an effective drug put out of their reach by the colleagues of the Regulatory Review Officer. Then they will know what it is like to be the confidant of a lethal outrage, while outside the clinic the world still turns for the unsuspecting, and nobody gives a damn.
—Dan Roentsch
1October 22, 2002. "Fox Chase Cancer Center Studies Breast Cancer Drug Made from 'Sea Squirts'". Philadelphia: the Fox Chase Cancer Center. Available from World Wide Web: (www.fccc.edu/news/2002/Sea-Squirt-10-21-2002.html)."Breast cancer, when caught early, often can be successfully treated, but fewer treatment options exist for women whose cancer has spread," said Lori J. Goldstein, M.D., director of the breast evaluation center at Fox Chase and principal investigator for the latest ET-743 study. "Since the beginning of time, we have turned to nature to find medicinal agents. This time, we're looking to the sea with hopes that the sea squirt drug can help us treat advanced breast cancer."
2Rumble, Warren F. letter of regulatory review officer to PharmaMar USA Vice President Flaircloth, Glynn T., 25 June 2001 [date released by FDA]. Available from World Wide Web (http://www.pharmcast.com/WarningLetters/Yr2001/June2001/PharmaMar0601.htm)
3Several of these papers are available from the World Wide Web. See for example http://www.mesotheliomaweb.org/marinecure.htm, and PharmaMar's European (hence beyond the reach of the Regulatory Review Officer) Website: http://www.pharmamar.es/en/prosci/facts_001.cfm
4American Cancer Society. "What Are The Key Statistics For Sarcoma?" Available on World Wide Web (http://www.cancer.org).
5Susan Fitzgerald, "Braving disease that can kill or maim in hours," Knight Ridder Newspapers. Available from World Wide Web (http://www.grandforks.com/mld/grandforks/news/nation/4447551.htm).
6"Killer Disease on Campus," Narr. Will Lyman. NOVA. PBS. 3 September 2002. Transcript available from World Wide Web (http://www.pbs.org/wgbh/nova/transcripts/2909_meningit.html).
7Adam Feuerstein, "ImClone Could Get Erbitux Approval Within a Year," TheStreet.com. (http://www.thestreet.com/tech/adamfeuersteing/10010676.html).
9Andrew Pollack, "Partners Promise New Tests of Cancer Drug," The New York Times, 4 October 2002.[Part of the Times' premium archive. Requires purchase.]
10The Nuremberg Code is available on the World Wide Web from the National Institutes of Health, Office of Human Subjects Research. (http://ohsr.od.nih.gov/nuremberg.php3)
Labels: erbitux, fascism, FDA, libertarian, meningitis, nuremberg code, Roentsch, statism, terminal illness
posted by Dan Roentsch at
7:50 PM
