Recognizing that there is a significant need to conduct studies in patients who have organ dysfunction, the Investigational Drug Branch performs studies of investigational agents just prior to potential licensing for therapeutic indications by the FDA. The primary goals and objectives of these study initiatives are outlined below:
The kidneys, as excretory, biosynthetic and metabolic organs, have a vital role in normal physiology. In the United States, approximately one in nine adults has chronic kidney disease (CKD) and a minority suffer from its terminal complication, end stage renal disease (ESRD). CKD is usually silent until its late stages, and without aggressive screening, detection may not occur until immediately before symptomatic kidney failure develops. A diagnosis of renal impairment has serious repercussions for many drugs excreted by the kidneys. Most obviously, renal impairment may decrease excretion of drugs or their metabolites, leading to accumulation and potential toxicity. But additionally, renal impairment has the potential to affect drug absorption, hepatic metabolism, plasma protein binding, and drug distribution. As renal impairment progresses from mild to moderate or severe, these changes become more pronounced.
Hepatic dysfunction is much more common than renal dysfunction in the oncology patient population, and its main functions—metabolizing drugs or promoting the excretion of unchanged drugs or metabolites in the bile—is crucial for may drugs. In the United States, drug-induced liver injury (DILI) is now the leading cause of acute liver failure (ALF), exceeding all other causes combined. Acknowledging that drugs have the potential to injure patients’ livers seriously—contributing to illness, disability, hospitalization, life-threatening liver failure, the need for liver transplantation and sometime causing death—the FDA and several other organizations are increasing efforts in this area.