Few NACCT Abstracts of Adverse Drug Reactions are Reported to MEDWATCH
Bruce Ruck, PharmD
Thelma Jennis MPH
Steven Marcus MD
New Jersey Poison Information and Education System
Newark Beth Israel Medical Center
Int J Med Toxicol 2000; 3(2): 4
The US Food and Drug Administration (FDA) has the statutory regulating authority to approve medications for use in the United States. Once approved by the Food and Drug Administration, medications are usually considered safe. Safety of medications is actually relative, one always has to consider a medications risk to benefit ratio. FDA approval occurs subsequent to clinical trials (also called pre-market testing) that demonstrate the relative efficacy and safety of the medication. Pre-market testing often fails to detect adverse drug reactions (ADRs). For evidence that pre-market testing fails to detect ADRs one only has to look at the list of medications removed from the market within a year or two of initial approval or the list of warnings that have been promulgated by the FDA about previously approved medications. Pre-market testing fails to detect ADRs for many reasons such as small sample size, short study duration, and restrictive inclusion/exclusion criteria.
Pre-market testing generally takes place in several hundred to several thousand patients. If an ADR is not common, no matter how serious, it may not be detected until FDA approved and used in a substantially greater number of patients. Most studies are of relatively short duration; days to months, very few last a year or more. If the adverse effect occurs after several weeks, months or years of continuous therapy it is evident that study duration of less time may not be sufficient to detect the adverse reaction. While strict inclusion and exclusion criteria are necessary to maintain the validity of a study, they also contribute to our knowledge deficit regarding a medication’s potential side effect profile. Most clinical trials exclude patients with multiple disease states or those taking multiple medications. Adverse effects, which occur as a result of a disease-medication interaction, may not become evident until many people with the interacting disease use the medication. The same concept holds true for adverse effects that occur as a result of a drug-drug interaction. This interaction may not be discovered until many patients are administered both drugs together. Other factors also contribute to our initial knowledge deficit about a medications potential side effect profile; these factors include the use of a medication in age groups not sufficiently represented in clinical trials and the use of doses outside of the range initially evaluated.
Once commercially available, information about a medication’s adverse effect profile arises from post-market surveillance. Post-market surveillance refers to the continued monitoring of a medications’ safety profile after FDA approval. Post-market surveillance relies upon the detection and "voluntary" reporting of adverse effects by health care professionals. The FDA’s latest program to improve post-market surveillance is MedWatch. MedWatch was introduced in June 1993 to replace a post-marketing surveillance program in place since 1961. MedWatch was introduced to improve a post-marketing surveillance program that was confusing, fragmented, and underutilized.
One goal of MedWatch is to detect trends in medication safety and to allow for appropriate action based upon these trends. MedWatch depends on the voluntary reporting of adverse effects by all health care professionals. Over 140 health care professional and industry organizations have signed on as MedWatch "Partners". These organizations include the American Association of Poison Control Centers, American Medical Association, American Society of Hospital Pharmacists, and the American College of Emergency Physicians. MedWatch partners help promote the four MedWatch goals:
- To clarify what should and should not be reported to FDA.
- To increase awareness of serious reactions caused by drugs or medical devices.
- To make the reporting process easy.
- To give the health community regular feedback about product safety issues.
Despite great efforts to improve post market surveillance many ADRs that would be of interest to the FDA go unreported. Because reporting is voluntary many health care professionals fail to report suspected adverse reactions to MedWatch. Reasons for not reporting are numerous and include:
- Not knowing what to report
- Not knowing how to report
- Reporting is considered too time consuming
- Concerns about liability
- Belief that someone else already made the report
- Belief that the ADR is a well recognized complication of the specific medication
It is presumed that abstract presentations of adverse drug reactions warranting a poster at the North American Congress of Clinical Toxicology Annual Meeting would be "unique" enough to warrant a report to MedWatch. The purpose of our study was to determine what percent of ADRs presented as a paper were reported to the FDA.
Two-hundred and fifty abstracts from posters presented at the 1998 North American Congress of Clinical Toxicology Annual Meeting were reviewed. Presenters of those that met the MedWatch reporting criteria were contacted to determine if the case was reported to MedWatch or the medication’s manufacturer. Reporting to the manufacturer was viewed as reporting to MedWatch because the pharmaceutical manufacturer is required to report to the FDA all adverse effects attributed to their products.
There were 24 abstracts presented which warranted MedWatch reporting. We made telephone contact with authors of 16 abstracts. MedWatch or the medication’s manufacturer was informed of 3/16 (18.75%) cases. Reports were not submitted for 11/16 (68.75%) cases and in 2/16 (12.5%) cases it was not known if the cases were reported. Reasons for not reporting included "no one suggested it", "we would have too many to report", "it is part of a legal case and it will be reported when it is over", and "no it is a dietary supplement."
Based upon these results it is evident that many suspected adverse effects do not get reported to MedWatch. One would have hoped that a case report warranting presentation at a national poison control/clinical toxicology symposium is unique enough to warrant a report to MedWatch.
Cases presented as part of poster presentations are an extremely important method of educating health care professionals about suspected adverse effects. Unfortunately, without a central repository for this information (the FDA) trends in adverse effects maybe missed. Trending of adverse effects that occur when a medication is administered/taken in a manner that is consistent with the product labeling or out side of the approved labeling is extremely important.
The FDA is most interested in receiving a MedWatch report if the adverse effect results in death, a life-threatening situation, and hospitalization or prolongs hospital stay and permanent disability. –Also of interest are cases when an adverse medication reaction is suspected of causing birth defects, miscarriage or death of a fetus.
With respect to reporting suspected adverse reactions to MedWatch or learning about warnings from the FDA, one can find valuable information at the FDA web site (www.fda.gov). Once at the Web site, warning letters related to adverse drug reactions, drug interactions, product recalls, and a MedWatch submission form can be found by entering the section called MedWatch. The section devoted to MedWatch is divided into several areas. The newest warning letters issued by the FDA can be found in the section titled "WHAT'S NEW THE PAST TWO WEEKS". Information greater than two weeks old can be found in the section called "Safety Information". In addition, this section also contains warning letters sent to health professionals and other safety notifications, medication labeling changes related to medication safety, information regarding recalls of fractionated blood & plasma products as well as FDA recalls and legal actions. A MedWatch submission form can be completed on line by entering the area called "How to Report".
Considering those attending/presenting papers at the North American Congress of Clinical Toxicology Annual Meeting are an "elite" group with a special interest in adverse effects to medications it was disappointing to find only 19% were reported to MedWatch. It is understandable that the rate of ADRs reported by the general medical community must be much lower.
Cases presented as part of a poster session are often considered "unique, rare occurrences, first time occurrences, etc." they often meet the reporting criteria of MedWatch. Based upon this information we believe that an increase in reporting can occur if the organizers of symposium actively encourage reporting to MedWatch. Along with the application for submission symposium organizers could include a MedWatch form or they could ask/remind those submitting cases that a MedWatch form should be completed.
Int J Med Toxicol 2000; 3(2): 4
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