Compassionate use offers access to unapproved drugs

By Jennifer M. Gangloff

Driven by reports of the next “breakthrough,” patients are increasingly trying to get experimental cancer drugs while they’re pending FDA approval—an often agonizing wait, says Richard Pazdur, MD, director of oncology drugs for the FDA’s Center for Drug Evaluation and Research.

For most patients, he and other experts say, the best and safest way to get experimental drugs is through a clinical trial. But not all patients are able to enroll in a trial. They may not meet eligibility criteria, they may live too far away, trials may have closed down or the trial may be filled to capacity.

For patients who can’t enroll in a clinical trial but lack effective treatment, “compassionate use” may offer an alternative. Compassionate use—not an official FDA term—is the general term for voluntary programs run by some drug manufacturers that allow patients to get experimental, or investigational, drugs before they’ve been approved by the FDA. There are two basic types of compassionate use programs:

Expanded access program (EAP). EAPs are typically designed to provide widespread access to a drug that has proven efficacy in clinical trials but is still awaiting FDA approval. They’re similar to standard clinical trials with a specific treatment plan and certain FDA requirements, but they have looser patient eligibility criteria. More than 23,000 U.S. cancer patients enrolled in an EAP for Iressa before it was FDA-approved, for example.

Single patient use. This program offers an experimental drug to an individual patient, rather than a group. The FDA approves these uses on a case-by-case basis. Decisions are based on other treatments already available and information about the drug’s efficacy and potential toxicities.

Trying to get an unapproved drug through a compassionate use program can be frustrating, confusing, time-consuming and often fruitless. That’s because there’s no central database of these programs, terminology varies greatly, drug companies may not have consistent procedures and federal policy is constantly evolving. In addition, many drug companies are hesitant to offer compassionate use because they foot most of the costs, experimental drug supplies may be in short supply, safety problems may arise that could hinder FDA approval and alternative access could reduce participation in federally required clinical trials, especially those that are randomized.

And compassionate use programs may not be appropriate for everyone, experts say. Before plunging into a hunt for a program, consider the reality of your situation, suggests Nancy Roach, chair of the treatment issues committee for the Marti Nelson Cancer Foundation, a patient advocacy group that works to expand access to new drugs.

“Some patients may first want to ask themselves how they want to spend the time they have left,” says Roach, who sees the emotional toll that unsuccessful efforts can exact on patients and their families. “Do they want to spend it banging on a pharmaceutical company’s door? Do they want to spend it yelling at the FDA and chasing down a drug they aren’t sure is going to work? If you have legitimate scientific evidence that you might be helped, that’s one thing. But if you’re running after a false hope, that’s another.

If you do pursue a compassionate use program, keep these tips in mind:

Know the criteria. To qualify for compassionate use, patients typically must have exhausted standard treatment options, be ineligible for clinical trials and have a debilitating or life-threatening illness. If you’re simply trying to avoid side effects posed by standard treatment, you’re likely to meet with FDA rejection.

Do the legwork. To track down compassionate use programs, check with drug companies, cancer advocacy groups and clinical trial listing services. If you’re not up to it, get help from family and friends to make calls and send e-mails.

Understand the law. Compassionate use programs are offered at the discretion of a drug company. The FDA can’t compel a company to give you a drug or contact a drug company for you. And it may be able to provide only very limited, if any, information about experimental drugs because of proprietary reasons.

Enlist the support of your doctor. Although you’re the one who may need to track down drug information and company contacts, it is your doctor who must actually get formal approval from the drug company and the FDA for use of the drug. Your doctor must also submit detailed paperwork about your situation, including your medical history and previous treatments. In some cases, the FDA can turn around an approval in just 24 hours. Your doctor may also need to get approval from an institutional review board.

Be persistent. If a drug company turns down your request for individual use, keep trying. Get in touch with the right official, such as the medical director for oncology clinical development, to plead your case. If you’re denied a spot in an expanded access program, check in regularly with the investigators or medical center for openings or new trials.

That’s how Suzanne Dreger, 37, got into an expanded access program for Gleevec in June 2000, a year before it was FDA-approved. “I called them, I e-mailed them, I bugged them,” says Dreger, a Virginia legal secretary who was diagnosed with chronic myelogenous leukemia in 1997. “The worst that can happen is they say no, and the best is that they get sick of hearing from you and let you in. Patients really need to be their own advocate—no one else will do it for them.”

The Overseas Option

If efforts for compassionate use are to no avail, some patients look abroad for drugs that have been approved ahead of the FDA. Federal law allows patients or their doctors to import unapproved drugs for personal use in certain circumstances. For instance, use of the drug must be limited to three months or less, it must not pose an unreasonable risk and a doctor licensed in the United States must oversee treatment, Dr. Pazdur says.

But with no guarantee that the drugs meet U.S. standards, safety may be a concern. “There’s a potential for toxicity and no benefit, and also a risk of false hope for some,” warns Anthony Tolcher, MD, director of clinical research for the Cancer Therapy and Research Center’s Institute for Drug Development in San Antonio, Texas, and also clinical professor of medicine at the University of Texas Health Science Center in San Antonio. “I often recommend they consider another experimental study instead.”