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« Previous: Appendix H: Statistical Analysis of Mortality in the FIAU/FIAC Clinical Trials
Suggested Citation:"Glossary." Institute of Medicine. 1995. Review of the Fialuridine (FIAU) Clinical Trials. Washington, DC: The National Academies Press. doi: 10.17226/4887.
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Glossary


ALT:

alanine aminotransferase, an enzyme present in liver cells and a marker of liver injury when present in quantity in the blood

amylase:

an enzyme that catalyzes the hydrolysis of starch into smaller molecules

ascites:

retention of fluid in the abdomen

AST:

aspartate aminotransferase, an enzyme present in liver cells and a marker of liver injury when present in quantity in the blood

AZT:

zidovudine, formerly known as azidothymidine, a synthetic thymidine analog that inhibits the human immunodeficiency virus that causes AIDS


CAH:

chronic active hepatitis

CFR:

Code of Federal Regulations

cholangiolitis:

inflammation of cholangioles, one of the fine terminal elements of the bile duct system

cholestasis:

stoppage or suppression of the flow of bile, having intrahepatic or extrahepatic causes

chorioretinitis:

inflammation of the choroid and retina

choroid:

the thin, pigmented, vascular coat of the eye; it furnishes the blood supply to the retina and conducts arteries and nerves to the anterior structures

cirrhosis:

liver disease characterized pathologically by loss of the normal microscopic lobular architecture, with fibrosis and nodular regeneration

CMV:

cytomegalovirus, a pathogen that causes chronic disease in immunocompromised but not immunocompetent patients

coagulation:

the process of clot formation

CRF:

clinical report form, used to record patient data, in summary form, in clinical trials


ddC:

dideoxycytidine, a nucleoside analog used in the treatment of human immunodeficiency virus infection

ddI:

dideoxyinosine, a nucleoside analog used in the treatment of human immunodeficiency virus infection

didanosine:

ddI


encephalopathy:

any degenerative disease of the brain

Suggested Citation:"Glossary." Institute of Medicine. 1995. Review of the Fialuridine (FIAU) Clinical Trials. Washington, DC: The National Academies Press. doi: 10.17226/4887.
×

FIAC:

fiacitabine, a pyrimidine nucleoside analog originally synthesized by Fox and his colleagues at Memorial Sloan-Kettering cancer center to be used in the treatment of herpes group virus infections (See figure 1, chapter 4)

FIAU:

fialuridine, the principal metabolite of FIAC, also a pyrimidine nucleoside analog

flare:

a rise in serum aminotransferases (AST and/or ALT) prior to normalization of liver enzymes, frequently associated with clearance of hepatitis B virus from the liver


Gilbert's syndrome:

an inborn error of bilirubin metabolism, probably autosomal dominant, a benign elevation of unconjugated bilirubin with no liver damage or hematologic abnormalities

glomerulonephritis:

a variety of nephritis (inflammation of the kidney) characterized by inflammation of the capillary loops in the glomeruli of the kidney


half-life:

the time that it takes for the concentration of drug in plasma or the amount of drug in the body to be reduced by 50 percent

HBV:

hepatitis B virus

HCC:

hepatocellular carcinoma

HCV:

hepatitis C virus

hepatic steatosis:

fatty deposits in the liver

hepatocellular steatosis:

fatty deposits within or around hepatocytes

hepatocyte:

a parenchymal liver cell, an essential element of the organ

hepatotoxicity:

the quality or property of exerting a destructive or poisonous effect liver cells

HIV:

human immunodeficiency virus

hyperbilirubinemia:

excessive concentrations of bilirubin in the blood, which may lead to jaundice

hypoalbuminemia:

an abnormally low albumin content of the blood

H3X-MC-PPPA:

FIAU study conducted on five hepatitis B virus-positive subjects at the New England and Galveston sites, sponsored by Eli Lilly. Referred to in this report as Trial PPPA.

H3X-MC-PPPC:

FIAU study conducted on 15 hepatitis B virus-positive subjects at the National Institutes of Health Clinical Center, sponsored by Eli Lilly. Referred to in this report as Trial PPPC.

H3X-MC-PPPG:

FIAU study conducted on 17 healthy males at the Lilly Laboratory for Clinical Research, sponsored by Eli Lilly. Referred to in this report as Trial PPPG.


ICD:

informed consent document

IND:

investigational new drug application

interferon:

a naturally occurring protein produced by lymphocytes and fibroblasts in response to chronic viral infection which has been used in the treatment of chronic hepatitis B virus infection since the 1970s

IRB:

institutional review board


jaundice:

yellowish skin

Suggested Citation:"Glossary." Institute of Medicine. 1995. Review of the Fialuridine (FIAU) Clinical Trials. Washington, DC: The National Academies Press. doi: 10.17226/4887.
×

lactic acidosis:

severe and rapidly progressing accumulation of lactic acid in the blood

laparoscopic cholecystectomy:

surgical removal of the gall bladder

leukopenia:

reduction in the number of leukocytes in the blood, the count being 5,000 or less

lipase:

glycerol-ester hydrolase; any of a group of widely occurring enzymes that catalyze the hydrolysis of ester linkages between the fatty acids and glycerol of the triglycerides and phospholipids


macrovesicular steatosis:

accumulation of fat droplets around the cells of an organ

membranoproliferative glomerulonephritis:

a chronic glomerulonephritis characterized by the mesangial cell proliferation and irregular thickening of the glomerular capillary wall

microvesicular steatosis:

accumulation of fat droplets within the cells of an organ

morbidity:

the extent and frequency of disease symptoms and their impacts on daily activities

mortality:

the frequency with which infection results in death

murine:

pertaining to or affecting rats or mice

myelosuppression:

suppression of bone marrow activity, resulting in a reduction in the number of platelets, red cells, and white cells

myopathy:

damage to the muscles in the arms and legs


NAI (No Action Indicated) letter:

from the Office of Compliance of the Food and Drug Administration to the investigators and/or sponsors to inform them that violations have been identified but that no action is required

NDA:

new drug application

neuralgia:

paroxysmal pain that extends along the course of one or more nerves

neutropenia:

a decrease in the number of neutrophilic leukocytes in the blood

nucleoside analog:

molecules similar to the building blocks of deoxyribonucleic acid [DNA] that become incorporated into the viral DNA as the virus divides, inhibiting and interrupting this replicative machinery

NIAID:

National Institute of Allergy and Infectious Diseases

NIDDK:

National Institute of Diabetes and Digestive and Kidney Diseases


OAI (Official Action Indicated) letter:

from the Office of Compliance of the Food and Drug Administration to investigators and/or sponsors intending to warn them of an impending action and that requires a response within 15 working days

OPPR:

Office for Protection from Research Risks


pancreatitis:

inflammation of the pancreas

pancytopenia:

deficiency of all cell elements of the blood; aplastic anemia

pathogen:

a specific cause (bacterium or virus) of a disease

peripheral neuropathy:

damage to the nerves in the arms and legs

Phase I study:

Usually the first stage in testing an investigational new drug application to the Food and Drug Administration, done to generate preliminary information on the chemical action and safety of the new drug, and it is usually not controlled

Suggested Citation:"Glossary." Institute of Medicine. 1995. Review of the Fialuridine (FIAU) Clinical Trials. Washington, DC: The National Academies Press. doi: 10.17226/4887.
×

Phase II study:

Usually the second stage of testing it is carried out on persons having the disease or condition of interest, determining the efficacy of the drug along with providing information on safety

Phase III study:

Usually the third and final stage of testing; it is concerned with assessment of dosage effects, efficacy, and safety, the design usually includes a control treatment, and the drug manufacturer or sponsor may request permission to market the drug for the indication or condition covered in the testing

proteinuria:

An excess of serum proteins in the urine; also called albuminuria

protocol:

the plan or schedule of events to be followed in a study or investigation or in an intervention program


R89-001:

FIAC study conducted on 12 human immunodeficiency virus-positive/cytomegalovirus positive subjects at the University of Washington and University of California at San Diego, sponsored by Oclassen Pharmaceuticals. Abbreviated throughout this report as R89.

R90-001:

FIAU study conducted on 42 immunodeficiency virus - positive/cytomegalovirus positive subjects at the University of Washington, University of California at San Diego, and the National Institutes of Health Clinical Center, sponsored by Oclassen Pharmaceuticals. Abbreviated throughout this report as R90.

R91-010:

FIAU study conducted on 24 immunodeficiency virus - positive/cytomegalovirus positive subjects at the National Institutes of Health Clinical Center, sponsored by Oclassen Pharmaceuticals. Abbreviated throughout this report as trial R91.


SGOT:

serum glutamic oxaloacetic transaminase; older term for AST

SGPT:

serum glutamic pyruvic transaminase; older term for ALT

steatosis:

fatty deposits

subcutaneous:

under the skin


thrombocytopenia:

decrease in the number of blood platelets

transaminase:

aminotransferase; class of enzymes present in serum and in various body tissues, especially in the heart and liver and released into the serum as a result of tissue injury


VAI (Voluntary Action Indicated) letter:

from the Office of Compliance of the Food and Drug Administration that requests a response from the investigators and/or sponsors within 30 working days of receipt with a proposal for correcting or preventing future problems or deviations

varices:

an enlarged and tortuous vein, artery, or lymphatic vessel

VZV:

varicella-zoster virus


WHV:

woodchuck hepatitis virus


zidovudine:

azidothymidine (AZT), a nucleoside analog used in the treatment of human immunodeficiency virus infections

Suggested Citation:"Glossary." Institute of Medicine. 1995. Review of the Fialuridine (FIAU) Clinical Trials. Washington, DC: The National Academies Press. doi: 10.17226/4887.
×
Page 266
Suggested Citation:"Glossary." Institute of Medicine. 1995. Review of the Fialuridine (FIAU) Clinical Trials. Washington, DC: The National Academies Press. doi: 10.17226/4887.
×
Page 267
Suggested Citation:"Glossary." Institute of Medicine. 1995. Review of the Fialuridine (FIAU) Clinical Trials. Washington, DC: The National Academies Press. doi: 10.17226/4887.
×
Page 268
Suggested Citation:"Glossary." Institute of Medicine. 1995. Review of the Fialuridine (FIAU) Clinical Trials. Washington, DC: The National Academies Press. doi: 10.17226/4887.
×
Page 269
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In June 1993 a clinical trial of fialuridine (FIAU), a promising new medication for hepatitis B, was abruptly terminated when one of the 15 out-patients participating in the National Institutes of Health (NIH) study was suddenly hospitalized with liver failure. Although all the remaining patients were contacted and told to stop taking their medication, six more subsequently developed severe toxicity. Five patients died, and two others were probably saved from death only by having liver transplants.

In response to a request from the Secretary of the Department of Health and Human Services, the IOM committee has analyzed the FIAU clinical trials, making recommendations for additional safeguards for the conduct of future clinical trials. This evaluation included the review of documents pertaining to investigational new drug submissions, protocols and consent forms from other clinical trials, as well as information available from other clinical and preclinical experience with compounds related to FIAU and its parent drug, fiacitibine (FIAC), which is metabolized to FIAU. The committee does not seek to affix responsibility for the adverse outcome of this NIH trial, but instead focuses on whether any rules or procedures governing the clinical trials process itself need to be changed, and if so, what burdens or costs such changes might place on future clinical trials.

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