Experts discuss rules for access to experimental drugs

The extent to which patients should have access to experimental therapies is a hotly contested issue, and courts and regulatory agencies have wrestled with the problems involved when an individual is willing to be treated with unapproved drugs at the potential expense of causing harm not only to the individual but to the clinical trial process itself.

Although individuals have a right to refuse treatment, "there is no corresponding right to demand treatment," said Ezekiel J. Emanuel, MD, PhD, chair, Department of Clinical Bioethics, National Institutes of Health. "The courts have been clear that there is no constitutional right to experimental drugs off protocol."

Although individuals have argued for access to unapproved drugs by citing the Fifth Amendment, which states that no person shall be deprived of life, liberty, or property without due process of law, patient access to a phase 1 drug requires others (eg, oncologists, drug manufacturers) to participate in obtaining the drug. In addition, permitting wide access to phase 1 drugs harms society by affecting the drug approval process, Dr Emanuel said. Widespread access to early-phase drugs can affect patient enrollment into clinical trials designed to more definitively test a drug's efficacy and safety, which can delay FDA approval of needed drugs.

A high rate of exposure to ineffective and potentially unsafe drugs is the result of allowing access to phase 1 agents, Dr Emanuel said. Of 100 phase 1 oncology drugs, only 9 successfully complete phase 3 studies, and only 5 eventually receive FDA approval.

Expanded-access programs are not in the best interests of scientific development, said Judith Ochs, MD, from AstraZeneca Pharmaceuticals. Only full approval demonstrates efficacy and an acceptable risk:benefit ratio, and an expanded-access program may compromise the validity of a registration trial for regulatory approval.

The end point in phase 1/2 trials of oncology drugs is usually response rate, which involves a judgment on the part of the investigators, rather than survival. In addition, safety data are more difficult to interpret in terminally ill patients, who are often the recipients of early-phase drugs.

Other potential problems involved when granting access to unapproved drugs include assurance of equity in drug distribution, adequacy of drug supply, and the effect that such access may have on clinical trials that involve other experimental agents being developed to treat the same disease.

Finally, once a drug available through expanded access gains approval, patients who qualified for access will need to obtain the drug through commercial means, which may restrict access to a drug that has already been demonstrated to be beneficial for a particular patient.

Ann Ferrell, MD, deputy division director, Office of Oncology Drug Products at FDA, said that new rules for expanded access are being considered by FDA and that these new rules will take into consideration the potential pitfalls of expanded access and the safeguards that must be in place.