A US court of appeals ruling—that terminally ill patients have no constitutional right to obtain experimental drugs proven safe in phase I trials—leaves the emotional issue as contentious as ever, medically, ethically, and legally.
WASHINGTONA US court of appeals rulingthat terminally ill patients have no constitutional right to obtain experimental drugs proven safe in phase I trialsleaves the emotional issue as contentious as ever, medically, ethically, and legally.
Last month, FDA saw protesters in front of its Rockville, Maryland, offices for the first time since the AIDS actions of the 1980s and 1990s. The demonstrators urged faster drug approvals, greater access to experimental drugs, and specifically, fast approval of Dendreon's prostate cancer agent Provenge (see photograph).
In a new twist, the demonstration included not only cancer patients and their supporters but also individual investors in Dendreon. The company is currently working with FDA to provide survival data on Provenge that could lead to the drug's approval.
Participating in the protest rally were members of the Abigail Alliance for Better Access to Developmental Drugs, which filed suit against the FDA in 2003.
On August 7, the full Circuit Court of Appeals for the District of Columbia ruled 8-2 against the Abigail Alliance.The decision overturned a 2006 ruling by a three-judge panel of the Circuit Court, which sided 2-1 with the Alliance, which plans to appeal the new decision to the US Supreme Court.
The Abigail Alliance is named for Abigail Burroughs who died of head and neck cancer and was denied early access to cetuximab (Erbitux). In its legal complaint, the Alliance and the nonprofit Washington Legal Foundation argued that FDA policy "violates the constitutional privacy and liberty rights of terminally ill patients," specifically the Fifth Amendment guarantee against deprivation of life without due process.
Writing for the Circuit Court majority, Judge Thomas B. Griffith said the use of potentially toxic drugs with no proven therapeutic value could hasten the deaths of patients, and patient self-preservation "cannot justify creating a constitutional right to assume any level of risk without regard to the scientific and medical judgment expressed through the clinical testing process."
In the British Medical Journal (335:478-479, 2007), two medical oncologists squared off on the question: Should terminally ill patients have the right to take drugs that pass phase I testing? Arguing "No," Dean Gesme, MD, of the Minnesota Oncology Hematology Professional Association, emphasized several points:
• More than 90% of drugs tested in phase I trials prove unacceptable, and of approved drugs, most are incremental improvements rather than life-saving advances.
• Expanded use of unapproved drugs found safe in phase I studies could reduce accrual to phase II and III trials, actually delaying new drug approvals, and erode clinical testing by "substituting enthusiasm and wishful thinking for evidence-based medicine."
• Issues of liability and oversight associated with expanded access programs could make physicians and institutions unwilling to participate.
• Many drug companies refuse to participate in such programs because of costs and concerns that anecdotal reports of toxicities from drugs used outside of clinical testing may delay their approval.
For the "Yes" side, Emil J. Freireich, MD, professor of leukemia and of laboratory medicine at M.D. Anderson Cancer Center, made the following arguments:
• Safety is not an issue because the drugs have completed phase I testing and patients are willing to accept the risks.
• Many patients want to participate in phase II trials but cannot meet strict protocol requirements. Why not provide these drugs on a compassionate basis?
• FDA and NCI have found that compassionate use accelerates drug development because physicians must collect data according to the research protocol and provide it to the drug sponsor.
• Expanded access does not damage clinical testing but improves the system by bringing physician scientists back into the drug development process.
Advanced cancer patients should have the privilege of all members of a free society, Dr. Freireich wrote"to decide their own benefit:risk ratio."