From Canada, the land of long health care queues, comes a genuinely promising idea for speeding new medicines into the hands of patients—a fast track approval process called progressive licensing. Which is exactly what the U.S. needs. In 2007, the Food and Drug Administration (FDA) approved only 19 new drugs, the lowest number since 1983. Last year saw a minor uptick to just 24 new medicines.
In 2007, Health Canada, the Canadian government's lead agency on health care issues, launched a national discussion on how to transform the country's drug approval system. Currently, the Canadian drug approval process operates much like the FDA's version does. Pharmaceutical companies submit new drug applications to regulators who then set out criteria for securing bureaucratic approval of the drug—including a series of clinical trials to prove that the medicine is safe and effective.
This venerable drug approval model focuses on prohibiting sales until new products have been carefully tested and then approved by regulators. The chief goal is to keep unsafe drugs from reaching patients. As we shall see, regulators are much less worried about mistakenly rejecting safe and effective drugs.
To keep unsafe drugs out of the market, new pharmaceuticals must undergo a series of clinical trials. Phase 1 trials, involving a few subjects, evaluate how a new drug acts in the body and looks for dangerous side effects. Phase 2 tests the new drug for effectiveness in a few patients. Phase 3 expands the trials to confirm effectiveness and to obtain further indications about risks versus benefits. Increasingly, regulators now ask for Phase 4 trials as well, which are post-marketing studies that evaluate the treatment's risks and benefits once the public has begun using it. Rare side effects frequently don't show up until the drug has been used by hundreds of thousands of patients.
Part of the domestic slow down in drug approvals comes from the fact that since the 1980s FDA regulators have more than doubled the number of clinical trials required to get a new drug approved from 30 to about 70. This increase in trials has raised the cost of getting a new drug through the regulatory maze to over $1 billion, thus limiting the number of new drugs that pharmaceutical companies can afford to pursue.
This is where progressive licensing could rescue our creaky pharmaceutical regulatory system. While the final regulations in Canada are still being hammered out, one exciting possibility is that drugmakers could submit some of their new medicines for approval after completing relatively fast and inexpensive Phase 1 and 2 trials. Such trials would provide preliminary information about a drug's safety and efficacy. In exchange for this fast track pre-marketing approval, drugmakers would agree to greater post-marketing surveillance of drug safety. Which means that patients using a new drug would essentially enroll in the equivalent of a Phase 4 trial. This post-marketing information would allow companies and regulators to continually adjust the balance of benefits and risks over the life cycle of new drugs. One important caveat is that such post-marketing scrutiny must not become as costly as the current system of pre-market regulatory review.
Following Canada's preliminary framework, progressive licensing would initially apply just to drugs that address previously unmet medical needs and in those instances where obtaining extensive clinical information is difficult (such as drugs that treat only a small numbers of patients with rare diseases). But why stop there? Canada's free-market Fraser Institute thinks progressive licensing has the potential to fix the current over-regulation of all drugs. Every beneficial drug also has accompanying risks, after all; the question is who gets to weigh the risks and the benefits.
Currently, regulators make the crucial decisions about the risks and benefits of treatment. But this leads to unbalanced benefit-risk evaluations. Remember that from the point of view of pharmaceutical regulators it's far more important to avoid a single highly publicized death from a new drug than it is to worry about the hundreds of unknown patients who die because of delays in approving new life-saving therapies.
In a 2007 report, the Fraser Institute looked at how progressive licensing could be transformed into a more radically open system that allows patients and physicians to evaluate the benefits and risks of new therapies rather than relying on the judgments of timid bureaucrats. In the report, Fraser's Brent Skinner looked at how the risks of new treatments compare to the risks of alternative treatments that the public already accepts.
For example, consider the case of the over-the-counter pain reliever ibuprofen versus the new drug Vioxx. A novel painkiller introduced in 1999, Vioxx was withdrawn from the market because it was found to increase the risk of heart attacks. But further research indicated that many non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, also increase the risk of heart attacks among users.
Both types of medicine effectively relieve pain, but Vioxx had the benefit of reducing the risk of gastrointestinal bleeding, which NSAIDs exacerbate. But who should weight the risk of dying from heart disease versus the risk of dying from bleeding ulcers versus effective pain relief for rheumatoid arthritis? One 1999 study estimated that there are 103,000 hospitalizations and 16,500 deaths in the United States due to complications from NSAID-associated gastric ulcers. As Skinner notes, a patient who is at high risk from gastrointestinal complications might well choose to take the cardiovascular risks associated with Vioxx. Why not let patients and their physicians have this risk information and choose for themselves?
Progressive licensing could modernize the current process from one where bureaucrats grant extensive permission before new drugs hit the market into a system based on initial indications of safety and effectiveness followed by ongoing risk evaluations. This would give patients greater say in their treatment, allowing those who willing to accept a certain amount of risk early access to the latest treatments, while risk-averse patients and physicians could wait until further information became available. It would also increase the scope for private groups—perhaps along the lines of the Underwriters' Laboratories certification process—to evaluate benefits and risks.
Progressive licensing might turn out to be just what the doctors (and patients) ordered for reducing the backlog of new drugs awaiting the nod from overly cautious regulators.
Ronald Bailey is Reason magazine's science correspondent. His book Liberation Biology: The Scientific and Moral Case for the Biotech Revolution is now available from Prometheus Books.