Kianna's Law
November 15, 2005; Page A22

Somewhere up there, Kianna Karnes is smiling. The 44-year-old Indiana mother's death in March from kidney cancer has helped to inspire a proposal in Congress to bring ethics and modern science to the drug approval process for terminal disease.

We wrote about Ms. Karnes earlier this year because she was being denied treatment with two promising therapies for kidney cancer. Two compounds -- one from Bayer and one from Pfizer -- had already shown unquestionable activity against that particularly deadly cancer. But Ms. Karnes did not meet the complicated eligibility criteria for clinical trials involving the drugs, and even if she had she might not have gotten treatment. The Bayer compound was being tested against a proverbial sugar pill and she might have ended up in the placebo arm of the trial (that is, with the sugar pill).

Bayer and Pfizer also did not have so-called "expanded access" or "compassionate use" programs to make these drugs available, before formal FDA approval, because of several regulatory impediments to that practice. For starters, companies can't charge patients on even a non-profit basis for compassionate use, even though manufacturing these novel compounds can be expensive.

Moreover, the FDA tends to dismiss any favorable data collected during compassionate use as unscientific, though it is quick to seize on negative data and count that against final approval. Finally, by creating compassionate use programs, companies risk making it less likely that patients will enroll in the placebo trials that the FDA too often demands before it will approve a drug. These barriers to therapy seemed inexplicable to Kianna and her family, and to us as well.

Now comes the cavalry, in the form of the Access, Compassion, Care and Ethics for Seriously-ill Patients Act (ACCESS), co-sponsored by Republican Senators Sam Brownback of Kansas and Oklahoma's Jim Inhofe. Their bill would create a three-tiered drug approval system that would ensure that future patients won't have to suffer the same frustrations and missed opportunities as Kianna Karnes.

Their most novel idea is to add an entirely new FDA status -- called "Tier 1 Approval" -- to the two current tiers usually referred to as normal and accelerated. Tier 1 would be a limited form of approval that would allow companies to sell promising drugs to terminally ill patients who have exhausted existing treatments and are not eligible for any more clinical trials. The logic here is that if drugs have shown themselves safe and effective enough in so-called Phase 1 trials for the FDA to approve giving them to hundreds or thousands of patients in Phase 2 studies, there is no good reason to withhold them from a broader patient population that has run out of other options.

"The decision for terminally-ill patients to take an investigational drug should be between the physician and patients, not government bureaucrats," says Senator Brownback. Notice that the physician would still be playing a determining role in the decision. It's not as if we have to worry about desperate patients being gulled into taking Tier 1 drugs by snake-oil salesmen.

By the same token, the market will impose its own discipline on companies applying for Tier 1, since they won't go through the expensive process of applying and building manufacturing capacity unless they've got some pretty convincing data to show to doctors.

The bill's other major provision would ban the use of placebo or "no treatment" arms in trials of treatments for terminal disease. Some will object that this will make it hard to do good science. But the truth is that the FDA's medical device division already knows how to interpret data without placebo controls. (Nobody gets placebo defibrillators in trials, for example.)

A ban on the practice would help force the research community to catch up with 21st century medicine, such as keeping electronic health records and tumor registries. "Modern methods would provide adequate control and historical data without the need to repeatedly measure disease progression and survival times of untreated patients," said the Abigail Alliance for Better Access to Developmental Drugs in a statement supporting the Brownback legislation. In short, the practice of placebo trials for terminal diseases is morally indefensible and unnecessary, despite what some at the FDA still say.

As it happens, Bayer cancelled the placebo arm of its kidney cancer trial shortly after our editorials about Ms. Karnes earlier this year. And both the Bayer and Pfizer compounds we wrote about are now being offered in expanded access programs. But dying patients shouldn't have to be spotlighted in the Wall Street Journal to prod the drug-control bureaucracy to action. Senators Brownback and Inhofe deserve credit for a proposal that would make rapid and easy access to developmental drugs the rule, not the exception.