Ways to Speed Treatments to Patients

by Food and Drug Administration (FDA)

Moviegoers in the '30s and '40s were regularly treated to the high drama of a dying patient whose only hope lay in an experimental drug — usually called a "serum" — that had to be flown through a raging storm, at night, to the patient's bedside. In the Hollywood scenario, the "serum" always arrived in the nick of time, the patient was saved, the brave young doctor was acclaimed a hero with a brilliant future, and the world got a miraculous new weapon in the battle against death and disease.

Music Up — Fade To Black — Roll Credits

Such movies are, of course, fantasy. But underlying their dated and, by today's standards, corny plot lines is the widely held belief that when nothing else can help, desperately ill patients ought to have access to investigational treatments that show some evidence of being useful. Concerned health professionals and consumers alike have long maintained that even though possibly important new drugs or biologicals haven't yet completed the complex and often lengthy path to FDA approval, physicians should nonetheless be able to use them in willing patients who can't benefit from established therapy.

And, in fact, thousands of people receive investigational products, not only in carefully controlled clinical trials, but also in innovative programs aimed at giving them all the medical help possible.

Using investigational agents in a sort of last-ditch effort to help desperately ill and dying patients is not new to medicine. FDA has permitted the emergency use of unapproved, investigational products for many years. Under the general rubric "compassionate use," the agency has permitted sponsors of investigational agents to provide them to doctors not involved in controlled clinical trials for use in individual patients who might be helped by the treatment.

In 1987, FDA changed its regulations on investigational new drugs (INDs) to specifically authorize treatment use of such agents. The term "Treatment IND" highlights the fact that an investigational agent is being administered not primarily to gain information about its safety and effectiveness, as in a controlled study, but to treat certain seriously ill patients.

The change in terminology is emblematic of a shift in the way FDA, the Congress, the pharmaceutical industry, health professionals, and health activists view the role of drug development and drug regulation in this country. All agree that a major goal of drug regulation must be to speed the journey from laboratory to bedside of important new drugs for devastating illnesses.

The shift involves more than just wider treatment use of unapproved agents. It also encompasses steps to accelerate FDA's process for reviewing applications to bring new drug and biological products to the market. Without compromising the approval requirements for safety and effectiveness of new drugs and biologics, FDA has taken numerous steps to shorten the time devoted to pre-approval drug testing. This streamlining of the process is geared to eliminating unnecessary, duplicative studies, and expediting the review of innovative agents for the most serious or life-threatening conditions.

Through published guidelines and meetings with sponsors, FDA reviewers help drug developers plan studies designed to generate the information FDA needs to make decisions about approvability. In addition, under a new congressional mandate, the agency will be able to collect user fees from product developers and manufacturers to cover the costs of expediting the review of prescription drug applications.

Treatment INDs

The first class of drugs to generate interest in treatment use outside formal clinical trials consisted of beta-blocking agents used in certain forms of heart disease. During the mid-1970s, many thousands of patients were treated with beta blockers for advanced, life-threatening heart and lung conditions for which no effective alternative treatment existed. In one instance, more than 600 cardiologists treated some 20,000 patients with the anti-arrhythmic drug amiodarone before it was approved for marketing as Cordarone in late 1985.

By far the most celebrated use of a Treatment IND involved expanding the availability before approval of zidovudine, commonly known as AZT, to people with AIDS. Initial (phase 1) testing of the drug in 33 patients with AIDS, carried out between July and December of 1985, yielded encouraging results. Phase 2 trials to assess the drug's safety and effectiveness began in February 1986. About 300 people with AIDS at several centers around the country were randomly selected to receive either AZT or a placebo.

These studies were abruptly halted in September 1986 when it was discovered that 19 patients receiving placebo had died, while only one death had occurred among those receiving AZT. Within a week of receiving this information, FDA authorized a treatment protocol for AZT. As a result, more than 4,000 AIDS patients were treated with AZT before its approval as the first anti-AIDS drug under the brand name Retrovir in March 1987.

Building on that and other experience with treatment protocols, FDA developed and issued in May 1987 regulations codifying the circumstances under which Treatment INDs can be granted. While the purpose is to make promising investigational drugs available as early as possible to patients with serious or immediately life-threatening diseases, the Treatment IND regulations also ensure that, despite possibly extensive treatment use of an investigational agent, carefully controlled trials will go forward to demonstrate the drug's safety and effectiveness.

About the Author

www.fda.gov
FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.