The powerful drug that the hospice doctor had given Roy Neill helped relieve his shortness of breath. But the medicine that eased the symptoms of the chronic obstructive pulmonary disease that is killing him was also causing severe constipation.
"It was a stressful time," said Neill, 67 years old.
A hospice doctor caring for Neill at his home suggested he try an experimental drug, methylnaltrexone, designed to treat the constipation. After some thought, Neill decided to participate in the drug trial, though it would take effort. He learned to inject himself with the drug and kept notes on how it affected him. For Neill, the drug worked within 20 minutes.
Hospices are emerging as a new setting for drug trials as demand rises for medicines to address the needs of dying patients. Progenics Pharmaceuticals Inc. (Nasdaq: PGNX), the small Tarrytown, N.Y., company seeking approval of methylnaltrexone, recently tested it among 287 patients, most of them in the final months of their lives and under the care of hospices. The constipation it aims to treat is often an agonizing side effect of opioid drugs such as morphine, commonly used to control pain in the terminally ill.
The "greatest medical need for a drug like this is in patients at the end of life," said Paul Maddon, the company's chief executive officer.
The study reflects growing interest in clinical research for such patients and a belief among hospice organizations and academic researchers that dying patients have unique medical needs and not enough information on how best to meet them.
But hospices pose especially thorny challenges for clinical research. The programs, seen as an alternative to high-tech, high-cost intensive care units where many patients in the United States spend their final days, typically offer physical and emotional comfort rather than cures, and are often ill-suited to handle the rigors of a clinical trial because they lack the research staff common in hospitals.
Ethics are another issue. Some doctors and researchers worry that hospice patients' ability to make informed decisions for themselves may be impaired.
"People are really vulnerable when they're coming to the end of their life," said Porter Storey, executive vice president of the American Academy of Hospice and Palliative Medicine. "They're willing to sign up for anything," he said. They may cling to the hope an experimental drug will cure them, for instance, or may simply want to please their doctors by entering a trial.
The academy recently updated its statement on ethical practices for conducting studies, citing an "urgent need" for more research but emphasizing that any burden on patients should be held to a minimum. For instance, because of the limits of such patients' energy, researchers should "justify the importance" of each patient interview or visit, the statement says.
Interest in clinical research for symptom relief is growing as the population ages and as new treatments keep those with illnesses such as cancer and heart disease alive longer. At the same time, hospice use is rising.
"There has been, for a long time, a desire to have more of (the sickest) people in trials," said Robert Temple, director of the Food and Drug Administration's office of medical policy. Such ill people, for instance, are often on many drugs at once and may have impaired kidney, liver or heart functions that lead them to respond to treatment differently from healthier patients, he said.
Hospice and palliative medicine became an official medical subspecialty in the United States last October, encouraging more research-oriented doctors into the field. Drug makers are also seeing an opportunity for new products.
Some of the studies involve drugs already on the market. A research team at San Diego Hospice, for instance, is conducting a trial involving lidocaine, a generic anesthetic, to find out whether giving the drug intravenously can control pain in cancer patients for whom drugs such as morphine aren't enough.
Four Seasons Hospice & Palliative Care in Flat Rock, N.C., started its own research department about two years ago, and last week began participation in a mid-stage study sponsored by GTx Inc. (Nasdaq: GTXI), a small Tennessee company testing a drug to treat the deterioration of muscle mass in cancer patients, said Janet Bull, the hospice's medical director.
Progenics is among the first companies to conduct a late-stage, multi-hospice trial to seek FDA approval for a new drug. The company tested whether methylnaltrexone relieved constipation among patients taking opioid drugs who were expected to die within six months.
Progenics and Wyeth (NYSE: WYE), a major pharmaceuticals company in Madison, N.J., that entered a partnership with Progenics after the trials were nearly completed, have submitted the results and expect the FDA to make a decision by late January.
Progenics designed two trials -- one involving a single injection of the drug or a placebo, and another over a two-week period. Both trials were short because it wouldn't have been ethical to keep such ill patients on a placebo for long, says Maddon, the Progenics CEO. Patients given a placebo were eventually given the medicine if they wanted it.
Recruiting hospices for the trials was difficult. Some lacked the facilities to securely store an experimental drug. Community Hospice of Northeast Florida, Jacksonville, says it participated only in the first trial because it didn't expect enough eligible patients to remain stable for the duration of the second.
Some hospice nurses were uncomfortable with the idea of their patients enrolling in drug studies -- at certain sites, they prevented patient recruitment, according to two researchers. Richard Krawiec, head of investor relations and communications at Progenics, says he and a colleague visited nurses at about a dozen facilities to encourage them to recruit patients.
Gaining consent from patients required sensitivity. "We made very clear we wanted to have a great deal of clarity that this was voluntary," Krawiec said.
Researchers at some facilities say they were startled by how much work it was to conduct the study. Progenics paid several thousand dollars per patient to hospices that participated -- a standard rate, said Maddon. Still, San Diego Hospice had to hire two additional nurses and an administrative assistant partway through, said Charles von Gunten, the physician who heads research there. The hospice received additional compensation from the company, he said, but still didn't break even. But he said participation was valuable because research helps improve patient care.
The results haven't yet been published in a peer-reviewed journal. If the drug is approved, Progenics and Wyeth eventually plan to seek approval for wider uses, including a pill form for patients with chronic pain.