Dying for Lifesaving Drugs
- From: thewesterner <mscowboy@xxxxxxxxx>
- Date: Sat, 28 Jul 2007 07:10:47 -0700
http://reason.com/news/show/120763.html
Dying for Lifesaving Drugs
Will desperate patients destroy the pharmaceutical system that
produces tomorrow's treatments?
Kerry Howley | Aug./Sept. Print Edition
Ten years ago, doctors drilled a hole into John Gotschall's skull,
inserted two catheters, and pumped a poison into his brain. Using a
child's morphine pump, the team of neurosurgeons pushed diphtheria
toxin into Gotschall's temporal parietal lobe over a period of four
days. Eight weeks later, they did it again, reusing the same cavity
and pumping in a slow stream of tissue-killing fluid.
Gotschall was not well. Shortly before he invited a team of surgeons
to experiment with his cerebral tissue, the 44-year-old municipal
worker had plowed his car into a snow bank on a Baltimore street. When
he woke up at the hospital, doctors told him he'd had a seizure at the
wheel. An MRI revealed the cause of that seizure: a tumor deeply
embedded in his brain tissue. There are different grades of brain
tumor, many of them slow-growing. Gotschall had glioblastula
multiforma (GBM), brain cancer in its most aggressive and deadly form,
and he likely had only months to live.
Gotschall's physicians initially ordered chemotherapy and radiation,
the same weapons with which doctors have fought cancers for decades.
Neither worked. After he exhausted the standard options, he started
searching for nonstandard ones. His neuro-oncologist pointed him to a
group of doctors at Johns Hopkins and a drug in development called
TransMID. TransMID had survived Phase I testing, in which researchers
evaluate a medication's safety and appropriate dosage, and was then in
Phase II, in which researchers begin to evaluate efficacy. Gotschall
finally caught a break: He qualified for entrance into the trial.
Along with 43 other patients, Gotschall would have a chance at a
radical new treatment that might add years to his life.
TransMID is a Trojan horse: The drug attacks the tumor under the
pretense of a gift. Tumors feed on iron they absorb from surrounding
tissue, and the drug delivers deadly, iron-wrapped diphtheria toxin
straight to the site of the disease. The method is meant to be more
precise than scooping out the cancerous tissue, a technique that can
be as clumsy as its cringe-worthy name, debulking.
The treatment proved immediately effective in the most dramatic way
possible. Gotschall's tumor simply vanished. TransMID's newest poster
child, he touted the treatment on CBS Morning News. "It is dramatic,"
Gotschall's neurosurgeon, John Weingart, told CBS. "I mean, there is
no question that this is an unbelievable response."
Ten years later, TransMID is still not available to the public. About
18,500 Americans will be diagnosed with GBM this year, and the median
patient will survive 14 months. Treatment has not advanced
significantly in the last 20 years, so GBM victims will be offered
more of the same: chemotherapy, radiation, and when possible, surgery.
TransMID entered Phase III tests, meant to confirm efficacy and
monitor the drug's side effects, last year. But most currently
diagnosed GBM patients probably will never know about the drug, and
most of those who do find out about it will not qualify for trials. If
TransMID ever does go to market, these patients will be dead by the
time it gets there.
For as long as there are lifesaving drugs in development, there will
be dying patients undaunted by the dangers of an unapproved treatment.
But within the strictures of the current regulatory regime, very few
patients--mainly those who, like Gotschall, meet the criteria for
clinical trials--are granted the freedom to risk their lives in the
face of certain death. Consider the conditions for admission to the
TransMID trial. "The tumor has to have grown 25 percent since the
patient's last MRI, but it has to be under five centimeters," explains
Patrick Rossi, a physician employed by Celtic Pharma, TransMID's
manufacturer. "It can't have grown into the ventricles or the brain
stem. The patients have to have failed every other treatment: chemo,
radiation, stereotopic radio surgery, any kind of oncology agent,
grandma's soup, voodoo, you name it."
To terminally ill patients who do not qualify for such trials, and
typically cannot receive drugs until they are deemed effective by the
Food and Drug Administration (FDA), this obsession with clinical
control can appear deadly and cruel. As TransMID trickles through the
FDA pipeline, GBM continues to kill thousands of Americans every year.
Most patients who don't meet the criteria for admission to clinical
trials will not be granted the right to risk their lives with a
developmental treatment.
Since the 1960s, when randomized, double-blind clinical trials became
a standard requirement for bringing new drugs to market, clinical
researchers have confronted the chaos of disease with the trappings of
a regimented, uncompromising order. Drug trials are rooted in
centralized authority: trial slots are numbered, subjects handpicked,
control groups maintained, patients monitored. Maintaining this level
of precision requires not only the cooperation of willing test
subjects, but the coercion of the general population. To preserve
pristine testing conditions, the federal government curtails our
freedom of exchange and our right to take risks. Ailing individuals
and drug companies are prohibited from trading in unapproved drugs,
and terminal patients forbidden to experiment outside a clinician's
watch.
This approach to drug testing is rife with serious ethical problems,
but the preconditions for meaningful change are mind-boggling. The
current clinical trial regime is cemented in place by legal
restrictions that prevent patients from waiving their rights to sue
and a regulatory regime that resists even incremental change.
Alternatives to the standard placebo-controlled, closed clinical
trials exist, but guarantees that such trials will lead to a drug's
approval do not. A system meant to facilitate innovation in drug
development is itself resistant to change.
With billions of dollars on the line, the clinical trial industry has
never been more powerful. But in an age of increasing patient
autonomy, the walls surrounding the drug testing system are under
assault like never before. An organization called the Abigail Alliance
for Better Access to Developmental Drugs is suing the FDA, claiming a
constitutional right to trade in lifesaving pharmaceuticals. The group
wants to crack open the system, to give patients and their doctors the
right to choose between taking experimental, often dangerous drugs and
dying untreated.
To the dismay of the medical establishment, bioethicists, and many
groups representing cancer patients, a federal appeals court has ruled
in the alliance's favor. As the case continues to wend its way through
the courts, doctors, researchers, and even patients warn that the suit
could bring the drug development process to a screeching, lethal halt.
Resurrection and Insurrection
The FDA runs on $1.5 billion a year, while the global clinical trial
industry is worth roughly $10 billion. The Abigail Alliance, based in
its founder's home in Fredericksburg, Virginia, subsists on $50,000 a
year in donations. Its one full-time employee is Frank Burroughs,
father of the late, eponymous Abigail.
Burroughs, now in his sixth year of advocacy, has lost many of his
most important co-members. After last year's ruling in the alliance's
favor, the FDA argued that the group no longer had legal standing to
sue it, since none of the patients who had signed the original
affidavits were still members. They were all dead.
The alliance launched its assault on the FDA in 2001, right after 21-
year-old Abigail Burroughs died while fighting for access to
developmental treatment for head and neck cancer. In 2003, Frank
Burroughs and his pro bono lawyers at the Washington Legal Foundation,
a public-interest litigation group, filed a federal lawsuit in D.C.
They maintain that terminal patients have a constitutional right to
lifesaving experimental drugs that have passed the first phase of FDA
testing--the phase that establishes the safety and tolerability of a
treatment. The right to self-preservation through access to
experimental drugs, the alliance argues, is a substantive due process
right, implicit in the Fifth Amendment principle that no person may be
deprived of life, liberty, or property without due process of law. The
Supreme Court has used substantive due process reasoning, which is
highly controversial among legal scholars, to recognize unenumerated
constitutional rights to abortion, to private sexual activity, and to
send children to private schools. The Abigail Alliance argues that it
also protects the right of terminally ill patients, acting on a
doctor's advice, to obtain potentially lifesaving medication when all
other alternatives have been exhausted.
The group's complaint was dismissed, but last year a three-judge panel
of the U.S. Court of Appeals for the D.C. Circuit overturned that
decision. "A right of control over one's body has deep roots in the
common law," Judge Judith Rogers concluded in the majority opinion.
"The prerogative asserted by the FDA...impinges upon an individual
liberty deeply rooted in our Nation's history and tradition of self-
preservation."
The appeals court decision drew little attention, but the media
coverage it did attract was almost uniformly negative. "A court makes
up a right," snarked the Washington Post editorial page. A June 2006
article in The New Republic said the court's logic would put us "back
in the snake-oil days," and The Journal of the American Medical
Association lamented "a new era of unapproved drugs."
The FDA sought a rehearing by the D.C. Circuit, and a 10-judge panel
heard the arguments of both sides in March. No matter how the court
rules, the Abigail Alliance expects its legal battle to end in the
Supreme Court.
After Burroughs, the man who spends the most time promoting the
Abigail Alliance's cause is a geologist named Steve Walker. In
December 2000, Walker and his wife of 20 years--Jennifer McNeillie,
also a geologist--were in the process of adopting a child abroad. The
two had paid an agency, were looking at pictures, and were preparing
to go to Russia to make their final arrangements. Before they got
there, Jennifer was diagnosed with Stage 4 colon cancer. At 45, she
was told she had a slim chance of making it to 50.
McNeillie's bleak prognosis coincided with a flurry of promising
research in colon cancer treatment. Three new drugs, Erbitux,
Eloxatin, and Avastin, were in development, and McNeillie decided that
the risks of being a test subject were worth taking. She would wait
years, her cancer progressing, for the chance to try one. There were
no Eloxatin trials in progress at the time, and Erbitux and Avastin
trials were both closed to new enrollment. "The drugs were simply
unavailable," says Walker. "We couldn't get into the trials."
In September 2002, a bedridden McNeillie was finally admitted into a
small Erbitux trial. "The drug resurrected her," says Walker. "We went
skiing in Colorado. We went hiking." Without the drug, cancer cells
that lined McNeillie's stomach would appear, expand, leak fluid.
McNeillie would blow up like a balloon every four days and have to go
to the hospital, looking six months pregnant, to be drained through a
catheter. On Erbitux, her worst side effect was a rash. She went back
to work.
Six months after she started taking the drug, doctors spotted a new
tumor on her colon. By the rules of the trial--rules set to ensure the
FDA would accept the results--McNeillie could no longer participate.
No trial meant no drug. When Walker pleaded with McNeillie's physician
to keep dispensing the drug, the doctor pleaded back: Giving out more
Erbitux could mean giving up his license to practice medicine.
Determined to dig up more Erbitux, Walker spent six weeks shuttling
between the drug's manufacturer, ImClone, and the FDA. ImClone
responded quickly, offering to set up an entirely new trial just for
McNeillie so her treatment would conform to protocol. It took ImClone
10 days to set up the trial. The FDA then delayed for two and a half
weeks, mulling approval. "This is to give the same drug the same way
by the same doctor," says Walker. "During this time my wife is dying.
She is tremendously suffering." At the same time, Walker was trying to
get his wife into an Avastin trial. She didn't qualify.
Six weeks after she'd been kicked out of the trial, McNeillie was
given a dose of Erbitux. She passed away after six months on the drug,
in June 2003. Eight months later, the FDA deemed Erbitux and Avastin
safe and effective treatments for colon cancer.
The Abigail Alliance has collected many such stories. There is David
Baxter, a high school student suffering from colorectal cancer, denied
admission to trials for a promising drug because he was too young to
qualify. He died at 17 in 2001. Alita Randazzo, also suffering from
colorectal cancer, spent years flying to France to get Eloxatin, which
had been approved there but not yet in the U.S. When Eloxatin stopped
working, she was told by her doctors that her last hope was Erbitux.
Trials for Erbitux had closed. She died in 2002, still fighting for
access.
A Hard ACT UP to Follow
Enraged patients have jolted the FDA into action before. In New York
in 1987, protestors from the AIDS Coalition to Unleash Power (ACT UP)
hanged an effigy of FDA chief Frank Young on Wall Street. Activists
complained that AIDS drugs were too slow in being approved and too
expensive when they went to market. A year later ACT UP brought 1,000
protesters to the FDA's headquarters, vowing to shut the agency down.
The FDA stayed open, and 180 protesters were arrested.
Graced with voluminous media coverage, AIDS activists found their
confrontational tactics rewarded. AZT had been rushed through the
process before the activists showed up at the FDA's doors, the
protease inhibitor Saquinavir was approved three months after it was
submitted for approval, and a similar drug, ritonavir, was approved 24
hours after an FDA panel recommended that it be allowed on the market.
It was as if they'd slipped the FDA a massive dose of Adderall.
In the early 1990s, under congressional pressure to reform, the FDA
introduced "fast track" regulations to speed review of certain drugs
and complex "expanded access programs" through which terminally ill
patients could potentially receive medication. In 1997 then-President
Clinton signed the Food and Drug Modernization Act, part of which
allowed individual patients to request access to developmental drugs.
But many of the gains applied exclusively to AIDS patients, and from
where Burroughs is standing, even the systematic reforms appear
inadequate. Setting up an expanded access program, he argues, is such
a bureaucratic nightmare that the program is "essentially
inoperative." The process involves a significant amount of paperwork
for the patient's doctor, who may not be aware of drugs in
development; the pharmaceutical company, which has no real incentive
to participate; and the FDA, which is not known for its alacrity in
tackling administrative tasks. Drugs aren't eligible for such programs
until late in the clinical trial process. Still, such programs do
exist and they are occasionally utilized. Two patients have won the
right to try TransMID through such a program.
As the heyday of activism passed and the AIDS movement matured,
pressure for radical change began to wane. The Abigail Alliance is no
ACT UP, and Walker and Burroughs look with envy upon the group's
ability to jam drugs through the FDA bureaucracy. "Originally, we
tried to get support from the AIDS community," Burroughs recalls.
"But we didn't. They had won their victory." The 1980s marked the
first time dying patients had risen against the FDA, and no movement
of similar strength has emerged since.
In its fight against a sclerotic system, the AIDS community had a
major advantage: It actually was a community. Organized around civil
rights, supported by the political left, noticed by the mainstream
media, AIDS patients formed a vocal, recognizable class. "Contrast
that with the class of patients who are terminal," says Walker. "There
are hundreds of cancers. These people have nothing in common. By the
time they're sick, they have no way of connecting to anyone else. They
don't have time to go to meetings and lobby the FDA. The only thing
they have in common is that the FDA stands in their way. And sometimes
they don't even know that."
It's more than a lack of organization that plagues the alliance.
Groups representing the victims of deadly diseases are often vocally
opposed to its agenda. The American Society of Clinical Oncology
submitted an amicus brief in the alliance's pending case-in support of
the FDA. In a September 2003 press release, Fran Visco, head of the
National Breast Cancer Coalition, announced that a victory for the
Abigail Alliance would "undermine scientific research and impede our
search for answers that will help everyone." The Leukemia & Lymphoma
Society, the National Childhood Cancer Foundation, and the National
Patient Advocate Foundation have all voiced their intention to side
with the government.
'Piles of Bodies'
While Burroughs and Walker believe they are tearing down senseless
bureaucratic obstacles, their opponents charge that the Abigail
Alliance is trying to hijack drug development the world over. Clinical
trials have been the primary way the medical establishment obtains
information about drug efficacy for the last 50 years. To its
detractors, the alliance seems prepared to cripple an ever-evolving
body of pharmaceutical research. In the interests of a few patients
suffering now, it is willing to cause an untold amount of damage to
patients yet to be diagnosed.
Trials conducted in the United States are the most rigorous in the
world, consisting of three distinct phases, typically involving
thousands of patients. Only 11 percent of drugs that enter clinical
trials are ultimately approved, and the numbers are markedly worse for
cancer drugs. Anyone who argues for the unencumbered right of patients
to take developmental cancer drugs must grapple with the fact that 94
percent of them will not work.
To sift the pharmaceutical gold from this vast bed of chemical silt,
drug companies need some type of trial system, and for trials they
will need patients. Trials are typically randomized, meaning that some
patients will receive the treatment and others will not. If patients
could simply obtain the medicines they wanted, they would have little
incentive to enter the clinical testing lottery.
"How do you take a rational person and get that person to enroll in a
double-blind, randomized clinical trial?" asks Steve Walker. "How do
you get people to do that? You give them no other choice. They're not
lives worth saving. They're lives worth using. If you can't get into
the trial, they can't use your life. They need two piles of bodies."
Mindful of medicine's dependence on test subjects, the alliance isn't
asking that all patients get access to development drugs. It's asking
that patients already denied admission to trials--patients like
Abigail Burroughs and Jennifer McNeillie--be able to buy the drugs
they're denied. And even this concession, argue their opponents, would
dismantle the clinical trial system.
The amicus brief submitted by the American Society of Clinical
Oncology argues that if people who didn't qualify for trials had
access to drugs, patients would have an incentive to appear
ineligible. Their physicians could easily help them game the system
by, say, ordering a round of chemotherapy, which disqualifies patients
for many Phase II and Phase III trials.
By that logic, Abigail Burroughs had to be denied treatment to protect
the integrity of the clinical trial process. Terminal patients who
cannot gain admission to trials still must be prevented from receiving
developmental drugs, lest future patients refuse to submit themselves
to randomized testing. "They need test subjects," says Walker, "and
patients are their only resource." Pull even a single thread, and the
whole information-aggregating web unravels.
This conflict has a way of pitting those without any hope of survival
against those with some chance at life. Take David Welch, co-founder
of the successful software company Telco Exchange. In 2004 doctors
found a tumor the size of a lemon in Welch's left frontal and left
temporal lobes. The 38-year-old chose to be aggressive, pursuing a
treatment so risky that three review boards rejected his request to
have the operation performed at their hospitals. The treatment was
successful, and Welch, now on his 19th round of chemotherapy to keep
the remaining cancerous cells at bay, is unambiguously positive about
the operation and his right to risk it.
Welch might seem the typical Abigail Alliance booster, eager to argue
for the right to experiment in the face of death, but he is deeply
ambivalent. "I medically inherit what has been given to me," he says.
"Statistically, I've got a time line of five to six years. The more
time I buy, the more time I have for clinical trials to play out. I'm
still open to arguments, but I fail to see how we can change the
process without breaking it down."
Welch also argues that even if pharmaceutical companies were allowed
to sell their drugs prior to approval, they have strong incentive not
to do so. Anything that happens to a patient taking a drug in
development could later be used to argue against approval, halting
manufacture and denying that drug to future patients. And under
current FDA regulations, patients cannot waive liability for
negligence. Whether they want it or not, patients must have the right
to sue, which means they may never be given the chance to take a risk.
If the Abigail Alliance wins its case, it will face additional legal
battles.
There is a serious argument to be made that the entire clinical trial
system is antiquated, that it is time to stop counting piles of bodies
and to start using more sophisticated measures of drug efficacy.
Biomarkers, substances whose presence in the body indicates a
particular disease state, could provide objective evidence on how a
drug is working on a particular patient. As such measures improve, the
need for placebos may lessen. "Clinical trials are very cumbersome,"
says Thomas Garvey, a gastroenterologist and former FDA supervisor who
has designed thousands of clinical trials. "Although they are not the
be all and end all. The science is evolving and getting better."
A March 2005 editorial in The Wall Street Journal advocated scrapping
placebo trials for cancer patients altogether, giving everyone access
to the drugs, and using advanced statistical methods to measure
patient progress versus the typical survival rate for a particular
cancer. This is the kind of change the Abigail Alliance hopes for, but
more incremental changes are already in play.
In an attempt to increase flexibility and reduce approval times, some
pharmaceutical companies have begun to conduct what are known as
"adaptive" trials. Standard trials are blinded: The findings remain
secret from researchers until each phase of the trial is over, and
they are conducted on general populations of patients with similar
conditions. Even after a standard trial has ended, it can be difficult
to know which patients within a population will respond most
positively or suffer the most severe side effects from a particular
drug.
Alternatively, adaptive trials allow researchers to analyze and
respond to data as it comes in, personalizing treatments and assessing
how patients with particular characteristics respond to particular
dosages. Researchers can tweak the trial design as they move forward,
perhaps dropping a method of treatment that proves unpromising or
adding more of one type of patient that seems to be responding well.
Trial flexibility may prompt shorter approval times and allow
companies to sort good drugs from bad more efficiently. "It's a
slightly less restrictive straitjacket," says Walker.
Drug development needs to move in lockstep with the regulatory regime,
and the FDA has signaled its openness to new trial design with its
"critical path initiative," a program meant to jump-start the process
of moving toward more sophisticated clinical trials. Its stated goal
is to "bring new scientific discoveries--in fields such as genomics
and proteomics, tissue engineering, imaging, and bioinformatics--to
bear on product development."
While the agency's potential for change is heartening, the critical
path initiative is widely acknowledged to be under-funded and lacking
in institutional support. For the foreseeable future, the system will
be one that pits David Welch against Abigail Burroughs, information
gathering aimed at helping future patients against current patients'
desire to live. Dying people will be treated as data points; other
dying people desperately want those data.
The View From 40,000 Feet
In February the Food and Drug Law Institute, a D.C. nonprofit that
promotes education on law and public policy, held a colloquium on the
Abigail Alliance's lawsuit that illustrated just how far outside the
medical consensus the alliance and its supporters really are. The
colloquium included high-profile lawyers, a specialist in
pharmacoeconomics, and Arthur Caplan, one of the world's most
prominent bioethicists. The only panelist clearly in favor of the
alliance's position was Scott Ballenger, the alliance's lawyer.
Most of the panelists expressed profound discomfort with the Abigail
Alliance's rights-based argument and its challenge to the regulatory
structure. Caplan argued that terminally ill patients are desperate
and therefore may be more in need of the FDA's paternalism than other
classes of patients. The panelists spoke of caution, of "giving
pause," of balancing risk between patient and society.
After hours of staid presentations and speeches before an audience of
100, Steve Walker approached the mike as an audience member. "You're
all approaching this topic from 40,000 feet," he charged, launching
into an impassioned retelling of his wife's decline. The panelists
looked nervously at their colloquium booklets. The moderator, shifting
in her seat, looked torn over whether to cut him off.
Such are the P.R. challenges of the Abigail Alliance. As lawyers,
medical professionals, and bureaucrats debate the optimal regulatory
structure, Walker and Burroughs want to supplement abstractions with
anecdote, to replace talk of test subjects with stories of dead wives
and daughters. But when they trade the language of clinical science
for that of loss and bereavement, they can come off as too invested to
be reasonable and too emotional to merit response. In the heavily risk-
averse culture of the FDA bureaucracy, talk of rapid, radical change
isn't even countered. It's just ignored.
Even more than the regulatory barriers, this deep-seated fear of
disorder works against the alliance's agenda. "I don't have a right to
fly somebody's experimental airplane," reasoned Bruce Chabner,
clinical director of the Cancer Center at Massachusetts General
Hospital, Boston, in the August issue of the New England Journal of
Medicine, "so why should I have the right to some drug that a company
has dreamed up?" In defending the status quo, Chabner apparently did
not pause to consider that cancer drugs, as opposed to airplanes, are
unlikely to fall out of the air and kill passersby. Nor are people
typically forced to choose between flying an "experimental airplane"
and certain death. The right to self-medicate is considered so absurd
that incoherence passes for analysis in respected medical journals,
while opposition is treated as hysteria.
Things weren't looking much better on March 1, the day the alliance
defended its case, for the second time, before the U.S. Court of
Appeals for the D.C. Circuit. Scott Ballenger began by stating the
alliance's claim: that "terminally ill, mentally competent adult
patients have a due process right to informed access to potential
lifesaving investigational new drugs determined by the Food and Drug
Administration to be sufficiently safe for expanding human trials,
where there are no alternative government-approved treatment options."
"That's an awfully specific right," barked Judge David Sentelle, less
than a minute into Ballenger's argument. "I may have gotten a thin
copy, but I had a hard time finding it in my copy of the
Constitution."
The FDA argues this very specific right has been "gerrymandered," its
boundaries improbably stretched and manipulated to fit the alliance's
very specific demands. In order to disrupt the existing legal
framework as little as possible, the alliance has settled upon a
narrowly defined right to lifesaving pharmaceuticals. "We have
described the contours of the right in terms of the present regulatory
regime," says Ballenger, "and we're not trying to destroy it." The
alliance concedes to the FDA that it has a compelling state interest
in protecting the integrity of the clinical process. It concedes that
the FDA has the right to deny dying people drugs that have not yet
been subjected to Phase I testing. But it still claims this very
narrow right is implicit in the concept of due process.
If terminal cancer patients do have a constitutional right to
lifesaving drugs, the limits of that right are hard to discern. What
does it mean to be "terminally ill," after all, and where is the line
between a lifesaving drug and a life-prolonging one? Could a suicidal
cancer patient claim she has a constitutional right to marijuana in
order to ease her pain? Does it make any sense to say a fundamental
right hinges on the FDA's determination that a drug has passed Phase I
testing? And if not, what does that say about the Controlled
Substances Act, the Supreme Court's recent rulings on medical
marijuana, and the FDA's role as medical gatekeeper?
Although the Abigail Alliance has chosen not to assert a broader right
of individual autonomy, the narrow right it claims seems to imply
profound change to U.S. law. "Wouldn't the right you're asserting here
also apply, then, to the right to therapeutic cloning, or to organ
purchase?" Judge Brett Kavanaugh asked a few minutes into Ballenger's
oral argument. "Don't we have to take into account the repercussions
of what you're asking for here?"
This is a slippery slope, and it alarms supporters of the status quo.
Once you argue that the government has no authority to deny Jennifer
McNeillie access to cancer drugs, that she has a constitutional right
to accept a certain level of risk, it becomes difficult to know where
the agency's authority stops and her autonomy begins.
Staying Power
John Gotschall's glioblastoma disappeared for five years after
TransMID, the Trojan horse, tricked the tumor into absorbing it.
Meanwhile, the drug lumbered along its tortuous road to approval. GBM
is a relatively rare disease, and TransMID has a tiny prospective
market. Celtic Pharma's Rossi estimates testing has cost more than
$600 million so far. And during the last 14 years, the drug has cycled
through no fewer than nine pharmaceutical companies in three
countries. Every time TransMID's backers are bought out, as often
happens in the industry, Rossi needs to justify the enormous costs of
clinical testing to new owners with new priorities. Time and time
again, an acquisition or merger has left the drug without funding, at
which point Rossi cries, pleads, and eventually brings the dead drug
back to life. He casts his relationship to TransMID as something out
of Night of the Living Dead. "My colleagues call me George Romero," he
jokes.
In January of this year, Rossi was busy scouring the globe in search
of eligible tumors. The planned Phase III trial would require 363
patients, of which Rossi had found only half. But in February TransMID
met with yet another obstacle. Celtic Pharma decided to terminate
Phase III testing "on commercial grounds," citing the unlikelihood
that the drug would meet efficacy requirements in the late-stage
patients it was testing on. TransMID's future is once again unclear;
Celtic may undertake new trials in patients with early-stage tumors,
sell TransMID to yet another sponsor, or terminate the drug's
development altogether. The 143 patients already enrolled in Phase III
testing will have to petition the company if they want more of the
drug.
As drug approval progresses in fits and starts, patients are liable to
fall into the gaps. When Gotschall's tumor returned in 2002, Phase II
of the clinical trials had concluded, and production of TransMID had
been halted during a merger. There was simply no new drug to give him.
Rossi petitioned the FDA for permission to dispense some TransMID left
over from Phase II, but the FDA would not grant permission to use the
remaining drug without potency and stability analyses. TransMID's
backers ordered the relevant tests. When those results were in, Rossi
reapplied for permission. The process took over 3 months. "By the time
we got approval to use the Phase II material," recalls Rossi, "they
gave John only days to live." Gotschall finally got the treatment, his
tumor rapidly growing. He died six months later.
In the nexus between men like Gotschall, who surrendered himself to
the whims of researchers, and Abigail Burroughs, who never got the
chance, lie uncomfortable truths about drug experimentation and
patients. At the very least, men like Frank Burroughs and Steve Walker
force us to acknowledge what we give up by insisting on the cold order
of randomized trials; they cast the trade-off in the starkest of
terms, because the lives of people they loved were part of what was
traded. Whereas patients once had the right to treat their bodies as
laboratories, their selves as subjects, the right to experiment on
individuals is no longer the province of the individuals themselves.
Patients fight for the right to be test subjects for others, and
consider themselves lucky to be chosen.
At the end of our last long interview, after Walker delivered his
usual hyperarticulate assessment of the cruelty of the clinical trial
system, capped off with another description of his wife's final days,
his voice grew suddenly weary. "God, I hate talking about this," he
said quietly. Patients of the present and future should hope he keeps
talking. Perfect information comes at a cost. And as Walker keeps
reminding researchers who don't want to listen, that cost does not
fall on everyone equally.
Kerry Howley is a senior editor of Reason.
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