UNFORTUNATELY, many health professionals do not think to report adverse 

events that might be associated with 

medications or devices to the Food and 

Drug Administration (FDA) or to the 

manufacturer. That needs to change, and 

the FDA is taking steps to encourage 

that to happen. 

Reports from health professionals of 

adverse events or product quality problems are essential to ensure the safety 

of drugs, biologicals, medical devices, 

and other products regulated by the 

FDA once they are introduced into the 

US market. 

Even the large, well-designed clinical 

trials that are conducted to gain premarket approval cannot uncover every 

problem that can come to light once a 

product is widely used. A new drug application, for example, typically includes 

safety data on several hundred to several thousand patients. If an adverse 

event occurs in perhaps one in 5000 or 

even one in 1000 users, it could be missed 

in clinical trials but pose a serious safety 

problem when released to the market. 

Moreover, patients taking marketed 

drugs in conjunction with other drugs 

may experience interactions not revealed during the premarketing phase. I 

In response to voluntary reports from 

physicians to the FDA or the manufacturer, the FDA has issued warnings, 

made labeling changes, required manufacturers to conduct postmarketing 

studies, and ordered product withdrawals that have ultimately prevented patient deaths and suffering. 

Adverse drug reports from physicians, 

for example, prompted the FDA to determine that torsades-de-pointes venFrom the Food and Drug Administration, Rockville, 

Md. 

A complete list of the participants in the Working 

Group appears at the end of this article. 

Reprint requests to Commissioner of Food and 

Drugs, Food and Drug Administration, 5600 Fishers Ln, 

Rockville, MD 20857 (Dr Kessler). 

JAMA, June 2, 1993-Vol 269, No. 21 

tricular arrhythmias could occur when 

the antihistamine terfenadine (Seldane) 

was taken in combination with the antifungal medicine ketoconazole or the 

antibiotic erythromycin.2 This episode 

also increased recognition that individual variability in drug metabolism can 

account for significant differences in patient responsel and underscored the importance of postmarketing studies and 

physician observations and reports. 

Other examples of FDA actions 

prompted by reports of adverse events 

include the 1986 recall of suprofen,a the 

1991 alert to health professionals on potentially fatal latex hypersensitivitY,4 the 

1992 boxed warning and alert to physicians regarding use of angiotensin-converting enzyme inhibitors during the second and third trimesters of pregnancy,5 

and, most recently, the recall of temafloxacin. 6 

Just as reports enable us to respond 

to serious adverse events, lack of reporting can delay problem detection. Silicone breast implants are one example. 

Although these devices have been on 

the market for some 30 years, only recently has evidence accumulated about 

a possible association with autoimmunelike disorders.7

,s If reports from physicians who diagnosed autoimmune-like 

disorders in patients with breast implants had been received years ago, the 

possible connection might have been 

identified much earlier. 

Aside from adverse events associated 

with specified vaccines(listed in the National Childhood Vaccine Injury Act9

), 

most reporting by health providers is 

voluntary. Manufacturers of drugs and 

devices and device distributors are required to report adverse events/O,ll and 

soon manufacturers of biologicals will 

face similar requirements. Device manufacturers and distributors are also required to report to the FDA product 

problems that may cause death or serious injury if the malfunction were to 

recur.n Health care facilities are required t(} report certain adverse events 

associated with devices.ll However, 

these groups, like the FDA, depend on 

health care professionals' surveillance 

and voluntary reporting. 

Although the FDA receives many adverse event reports, these probably represent only a fraction of the serious adverse events encountered by providers. 

A recent review article l2 found that between 3% and 11% of hospital admissions could be attributed to adverse drug 

reactions. Only about 1% of serious 

events are reported to the FDA, according to one study. I;) 

There are probably several reasons 

why some serious events are not reported to either the FDA or the manufacturer. First, when confronted with 

an unexpected outcome of treatment, 

physicians may not consider drug-induced or device-induced disease, but 

rather consider the event to be related 

to the course of the disease. 

Unfortunately, this may be due to the 

limited training medical students receive 

in clinical pharmacology and therapeutics. A 1985 survey ofUS medical schools 

found that only 14% of them had required courses in core skills and principles oftherapeutic decision making and 

clinical pharmacology. Of the remainder, 87% taught only a few hours of 

clinical pharmacology, and most of the 

teaching occurred in the early years of 

medical training.14 

Anotherfactor inhibiting physician reporting is that it is not an ingrained 

practice-it is not in the culture of US 

medicine to notify the FDA about adverse events or product problems. In 

other countries such as the United Kingdom, adverse drug reporting is more 

frequent. 15 A patchwork of reporting 

forms and systems may make it difficult 

to file reports in the United States and 

may discourage even the most conscientious professionals. Finally, physiIntroducing MEDWatch~Kessle 2765 

Reprinted from JAMA ® The JoumlJl of the American Medical Association
 


June 9, 1993 Volume 269
 


Copyright 1993. American Medical Association
 


• you're not certain the product caused the
 


event
 


• you don't have all the details 

Report product problems - quality, performance 

or safety concerns such as: 

• suspected contamination 

• questionable stability 

• defective components 

• poor packaging or labeling 

event with a device and it occurred in a facilrty out

side a doctor's office, that facility may be legally required 

to report to FDA and/or the manufacturer. Please notify 

the person in that facilny who would handle such reporting. 

Confidentiality: The patient's identity is held in strict 

confidence by FDA and protected to the fullest extent of 

the law. The reporter's identity may be shared with the 

manufacturer unless requested otherwise. However, 

FDA will not disclose the reporter's identity in response to 

a request from the public, pursuant to the Freedom of 

Information Act. 

Left and above, portions of the new MEDWatch reporting form. 

cians may be unclear as to what adverse 

reactions should be reportedto the FDA. 

Mindful of these problems, the FDA 

has just completed an overhaul of the 

adverse event reporting system. This 

month we are announcing our new system called MEDWatch: The FDA Medical Products Reporting Program_ (Adverse events associated with vaccines 

will continue to be reported through the 

Vaccine Adverse Event Reporting System [VAERS], a joint program of the 

FDA and the Centers for Disease Control and Prevention.9) 

This new system encourages health 

care professionals to regard reporting 

as a fundamental professional and public health responsibility. It was developed with the enthusiastic support of 

the medical community, and its success 

will depend on close cooperation among 

the FDA, the medical community, and 

industry to identify and report adverse 

events and problems with medications 

and devices. 

The FDA recognizes that the confidentiality of the identities of both providers who report adverse events and 

patients is an important concern ofhealth 

professionals. To encourage reporting, 

the FDA carefully protects the identities of providers who report and patients contained in FDA records and 

will not release such information to the 

public. Unfortunately, during the course 

oflitigation manufacturers have increasJAMA, June 2, 1993-Vol 269, No. 21 

ingly been asked to reveal the identities 

of those reporting adverse events and, 

in some cases, even the identities of patients. The FDA believes that maintaining the confidentiality of these individuals is extremely important, and it has 

participated in a number of court cases 

vigorously opposing release ofthe names 

of those involved in adverse event reports. To date, we have been successful 

in maintaining the confidentiality ofthis 

information in all the cases in which we 

have been involved_ Nevertheless, we 

are considering whether additional actions may be appropriate to further 

strengthen our ability to safeguard the 

confidentiality of this information. 

Our goal in introducing MEDWatch 

is to underscore the responsibility of 

providers to identify and report adverse 

events that may be related to FDAregulated products. To that end, we want 

to (1) make it easier for providers to 

report serious events, (2) make it clear 

to physicians and others what types of 

reports the FDA wants to receive, (3) 

more widely disseminate information on 

the FDA's actions that have resulted 

from adverse event and product problem reporting, and (4) increase physician understanding and awareness of 

drug- and device-induced disease. 

HOW TO REPORT 

Under the MEDWatch program, the 

separate forms previously used to re

discovery that the latex-cuffed barium 

enema tips used to perform many barium enema procedures provoked lifethreatening allergic responses in some 

patients.4 When the problem was first 

recognized, practitioners typically believed that patients were reacting to the 

barium sulfate or to other medications 

used in the procedure, and therefore adverse incidents were initially reported 

as barium sulfate reactions to the Center 

for Drugs. The new one-page form asks 

reporters to indicate concomitant devices as well as the suspect drug and 

other drugs used in the procedures. Using the new form might have decreased 

the follow-up time required by FDA officials, the time needed to identify latex 

as the problem, and the time until the 

medical community was alerted. 

The unified reporting form (Figure) will 

be available in several publications, including the Physicians' Desk Reference, 

the FDA Medical Bulletin, and AMA 

Drug Evaluations. A 24-hour-a-day, 

7-day-a-week toll-free number, (800) 

FDA-1088, is also now available for providers who want to request forms or obtain the new FDA Desk Guide to Adverse 

Event and Product Problem Reporting. 

Providers will no longer be expected to 

send different reports for devices and 

medications to different addresses at the 

FDA; there will now be a single mailing 

address for these reports. In addition, 

health professionals will be able to report 

electronically by computerby calling (800) 

FDA-7737 and responding to the questions that appear on the screen. Reports 

can be also sent to the FDA by fax ([800] 

FDA-0178) or by regular mail using the 

self-mailer included in the form. 

In addition to reporting adverse 

events to the FDA, reports can also be 

sent to manufacturers, which are required by law to forward reports to the 

FDA.IO,ll If the event has occurred in a 

health care facility, reports of problems 

with medical devices should also be filed 

with that facility, which legally must 

Introducing MEDWatch-Kessler 2767 
y 

fect; they are not expected to establish 

the connection or even to wait until evidence seems compelling. Reports should 

be alert of possible associations. Combined with other reports, follow-up, and 

results of epidemiologic studies or new 

studies undertaken, the FDA can evaluate these initial suspicions. 

On the other hand, the FDA does not 

want providers to report every adverse 

reaction observed; this would not be practical for the practitioner or useful to the 

FDA. The FDA's goal is to increase reporting ofserious events, not all adverse 

events. What should be reported are 

those cases in which the physician suspects that an FDA-regulated product was 

associated with a serious outcomedeath, a life-threatening condition, initial 

or prolonged hospitalization, disability, 

or congenital anomaly, or when intervention was required to prevent permanent impairment or damage. 

Although traditionally problems with 

devices are associated with products that 

are defective or malfunction, adverse 

events can occur with a device even when 

no malfunction or defect is recognized, 

for example, hypersensitivity to latex4 

or dialyzer germicides. 17 

References 

1. Peck CC, Temple R, Collins JM. Understanding 

consequences ofconcurrent therapies..lAMA. 1993; 

269:1550-1552. 

2. Honig PK, Wortham DC, Zamani K, Conner DP, 

Mullin JC, Cantilena LR. Terfenadine-ketoconazole 

interaction: pharmacokinetic and electrocardiographic consequences. .lAMA. 1993;269:1513-1550. 

3. Rossi AC, Bosco L, Faich GA, Tanner A, Temple 

R. The impOltance ofadverse reaction reporting by 

physicians: suprofen and the flank pain syndrome. 

.lAMA. 1988;259:1203-1204. 

4. Stehlin D. When rubber rubs the wrong way. 

FDA Consumer. 1992;26:17-21. 

5. Gelb LN, ed. Dangers of ACE inhibitors during 

second and third trimesters of pregnancy. FDA 

Med Bull. 1992;22(1):2. 

6. Rheinstein PH. Reporting of adverse events: a 

key to postmarketing drug safety. Am Fam Phys. 

1992;46:873-875. 

7. Press RI, Peebles CL, Kumagai Y, Ochs RL, 

2768 JAMA, June 2, 1993-Vol 269, No. 21 

of such problems. 19 While pharmacists 

or risk managers are ofLen the ones in a 

position to observe these problems, physicians who become aware of such problems should bring them to the FDA's 

attention by calling (800) FDA-1088 and 

submitting a report. 

One recent example of the importance 

of this type of report is the possible link 

reported between hyperkalemia observed 

in two patients in a medical center intensive care unit and two enteral feeding 

products. The university's laboratory 

analysis demonstrated that the products 

had a potassium content about twice that 

specified on the label. The FDA follow-up 

of this report revealed that all product 

lines of the manufacturer contained potassium values of 150% to 250% of the 

declared amount. Because these products 

are frequently used as a sole source of 

nutrition, and sometimes in patients with 

compromised renal function, the FDAinitiated a recall of the product. 

PROVIDE PHYSICIAN INFORMATION 

MEDWatch is aimed at facilitating 

reporting by providers, but we also want 

to better inform providers about regulatory actions taken by the FDA in reTan EM. Antinuclear autoantibodies in women with 

silicone breast implants. Lancet. 1992;340:1304-1307. 

8. Dunn KW, Hall PN, Khoo CTK. Breast implant 

materials: sense and safety. Br .I Plast Surg. 1992; 

45:315-321. 

9. Nightingale SL. New system for reporting of 

vaccine adverse events. .lAMA. 1990;264:2863. 

10. Johnson JM, Barash D. A review of postmarketing adverse drug experience reporting requirements. Food Drug Cosmetic Law J. 1991;46:665­

671. 

11. Medical Devices; Medical Device, User Facility, Distrib'utor, and Manufacturers' RepOIting, Certification, and Registration. Rockville, Md: Dept of 

Health and Human Services, Food and Drug Administration; 1991:60024-60039. 21 CFR parts 803 

and 807 (docket No. 91N-0295). 

12. Beard K. Adverse reactions as a cause of hospital admissions in the aged. [h~lg Aging. 1992;2: 

356-367. 

uate possible adverse events. As part of 

that effort we plan to hold a conference 

for health care professionals and FDA 

officials to help poise practitioners to 

recognize drug- and device-induced 

problems when they occur, and thereby 

increase participation in the MEDWatch 

program. 

MEDWatch is an important program 

that we hope will significantly improve 

our ability to monitor the safety of products we regulate and to take necessary 

actions swiftly and effectively. Perhaps 

most important, we hope MEDWatch will 

encourage an increased sense of responsibility among physicians and other health 

care providers about reporting adverse 

events and product problems. We are eager to work closely with the medical community to ensure the program's success. 

Leaders of the Working Group include the following: Sharon Natanblut, MPA; Dianne Kennedy, 

MPH, RPh; Eliot Lazar, MD; Peter Rheinstein, 

MD, JD, MS. Members of the Working Group 

include Chuck Anello, SeD; Dave Barash, RPh; 

Ilisa Bernstein, PhannD; Ross Bolger, RPh; Kay 

Cook, JD; Mary Pat Couig, RN, MPH; JetTy Donlon, MD, PhD; Joyce Johnson, DO, MA; Catherine 

Lorraine, JD; Tom McGinnis, RPh; John Nazario, 

RPh; Stuart Nightingale, MD; Carl Peck, MD; 

Mary Pendergast, JD; Suresh Rastogi, PhD; Chet 

Reynolds, MBA; Renie Schapiro, MPH; Linda 

Tollefson, DVM; Ann Wion, JD. 

13. Scott HD, Rosenbaum SE, Waters WJ, et al. 

Rhode Island physicians' recognition and repOlting 

of adverse drug reactions. RIMed J. 1987;70:311­

316. 

14. Griffin JP, Weber JCP. Voluntary systems of 

adverse reaction reporting, part II. Adv [h~l React Ac Pois Rev. 1986;1:23-55. 

15. Nierenberg DW. Clinical pharmacology instruction for all medical students. Clin Pharm Ther. 

1986;40:483-487. 

16. Accreditation Manual, 199:>. Oakbrook Terrace, Ill: Joint Commission on Accreditation of 

Healthcare Organizations; 1993. 

17. Gelb LN. Precautions needed for dialyzer germicides. FDA Med Bull. 1993;23(1):7. 

18. Kennedy DL,JohnsonJM, Nightingale SS. Monitoring of adverse drug events in hospitals. .lAMA. 

1991;266:2878. 

19. Bolger G, Goetsch R. Monitoring drug product 

quality. Am Pharm. 1992;NS32:47-50. 

Introducing MEDWatch-Kessler 

Printed and Published in the United States of America