Adverse drug experiences

A case is a basic unit of drug safety surveillance. It is used to assure, to the greatest extent possible, the safety of approved drug products that are still in use. The basic unit of all postmarketing safety submissions is the adverse drug experience case , which is an individual adverse drug experience. 

The number on the outside of the case is required to be numeric or alphanumeric, not the name of the patient. Patient names are not permitted to be publicly disclosed in the context of a MedWatch report according to 21 CFR 21.63(f). The initial report is the first reported information received by the company about an individual s adverse drug experience. There must be a prompt attempt to obtain follow-up information about each initial report. The attempt(s) are made according to the company s written procedures. If the written safety procedures are not followed, the safety reports are not appropriately submitted, or the safety records are not appropriately kept, FDA has the authority under Section 80 of Part 315 to withdraw the market NDA. The follow-up report is the format for submitting additional information about an experience. Each case regards only one individual unless the experience is both temporally and clinically unrelated to a second event experienced by the same person taking the same drug product. 

Postmarketing adverse drug experiences are reported to a drug company by the public via regulatory authorities, literature, attorneys, consumers, and health... 

Keller, W.C., Bataller, N. and Oeller, D.S. (1998). Processing and evaluation of adverse drug experience reports at the Food and Drug Administration Center for Veterinary Medicine. 

Synonyms of adverse reactions generally include adverse medical effects, untoward effects, side effects, adverse drug experiences, and adverse drug reactions. Specific distinctions among some of these terms may be defined operationally. For example, the term adverse reaction is used to denote those signs and symptoms at least possibly related to a medicine, whereas the term adverse experience is used to include nonmedicine-related medical problems in a trial such as those emanating from trauma or concurrent illness. Distinctions among side effects, adverse events, and adverse reactions are illustrated in the definitions of the two former terms. 

Buchanan, J.F., and C.R. Brown. Designer drugs. A problem in clinical toxicology. Medical Toxicology and Adverse Drug Experience 3, 1988. 1-17. 

Adverse drug event (or adverse drug experience) (ADE)... 

Although 2-PAM is an FDA-approved drug, data submitted to the FDA to obtain approval are proprietary and were not released when requests for them were made to the FDA and to the manufacturer. A report of the FDA Adverse Drug Experiences Monitoring Program (October 30, 1983) contained one adverse reaction (hypotension following 1 g by intravenous Injection). 

Additional serious or more frequent adverse drug experiences in a subpopulation of patients... 

In a placebo-controlled study of 1142 hypercholestero-lemic patients treated with pravastatin for 8-16 weeks, the numbers of adverse drug experiences were similar in the treated and untreated individuals (1). Rash was the only adverse clinical event that was different (4.0 versus 1.1%). However, in the same patients withdrawal of therapy during follow-up was thought to be necessary in 3.2% of those given pravastatin alone. Myopathy was observed in one instance only, and increases in creatine kinase activity in those taking pravastatin did not differ significantly from controls. There were marked persistent increases in transaminases in 1.1%, with no cases of symptomatic hepatitis. Pravastatin is believed to have a particularly low potential for nervous system-related adverse effects, as it has not been shown to enter the cerebrospinal fluid, and clinical experience suggests that muscle toxicity occurs less often with pravastatin than with lovastatin (2). 

Periodic adverse experiences reports These reports must be submitted quarterly for the first 3 years after approval of the product (within 30 days of the end of the quarter) and annually (within 60 days of the anniversary of the approval date) thereafter. Periodic adverse drug experience reports should present a narrative overview and discussion of the safety information received during the reporting period. 

Postmarketing Reporting of Adverse Drug Experiences, March 1,1992. Center for Drug Evaluation and Research (CDER). Guidance for Industry. Conducting a Clinical Safety Review of a New Product Application and Preparing a Report on the Review, Nov. 1,1992. 

Johnson, M., 6c Barash, D. (1991). A review of postmarketing adverse drug experience reporting requirements. Food, Drug, and Cosmetic Law Journal, 46, 665-672. 

Life-threatening adverse drug experience means any adverse drug experience that places the patient or subject, in the view of the investigator, at immediate risk of death from the reaction as it occurred, i.e., it does not include a reaction that, had it occurred in a more severe form, might have caused death. 

Postmarketing reports of adverse drug experience, including the 15-day alert reports and the periodic drug experience reports, should be submitted, unbound, in duplicate, to ... 

When a serious adverse drug experience occurs, the investigator will provide the following information ... 

Adverse drug experiences that are both serious and unexpected, whether foreign or domestic, must be reported to the FDA as soon as possible, but no later than 15 calendar days after initial receipt of the information (15-day Alert... 

Koren G.The nephrotoxic potential of drugs and chemicals. Pharmacological basis and clinical relevance. Medical Toxicology and adverse drug experience 4 59-72,1989. 

Leikin JB, Krantz AJ, Zell-Kanter M, Barkin RL, and Hryhorczuk DO (1989) Clinical features and management of intoxication due to hallucinogenic drugs. Medical Toxicology and Adverse Drug Experience 4 324-350. Odeleye OE, Watson RR, and Eskelson CD (1993) Enhancement of cocaine-induced hepatotoxicity by ethanol. Drug and Alcohol Dependence 31 253-263. 

Saxena K (1989) Clinical features and management of poisoning due to potassium chloride. Medical Toxicology and Adverse Drug Experience 4 429—443. 

Review the reports of previous inspections, reports of adverse drug experiences and complaints, if any exist, as investigations and corrective action taken by the manufacturer should be verified during inspections. 

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