Adverse Drug Reaction Surveillance: Practical Methods for Developing a Successful Monitoring Program

Josephine A. Vitillo, PharmD, BCPS, CGP

Disclosures

December 18, 2000

In This Article

How to Increase Your Detection of ADRs

The ASHP has reported the barriers to improved monitoring and reporting of ADEs (Table 1).[10] Below are recommendations to improve detection of ADRs and overcome these barriers.

  1. Make it Easy - Make it easy to report ADRs. The more complicated the process, the less likely personnel will comply. Anything that creates more paperwork will not succeed.

  2. Hot Line - Set up a telephone hot line to report ADRs. The designated line should allow the reporter to simply provide the patient's name, location, the suspected drug, and reaction. The pharmacy department would then evaluate the patient's medical record. A pharmacist need not man the telephone. It could be equipped with an answering machine or voice mail that is checked daily by the pharmacy department, thereby minimizing the time the pharmacist spends on the telephone.

  3. Fax Line - A fax line could be set up to allow reporters to fax pertinent information to the pharmacy department alerting of an ADR. As many institutions routinely fax physicians' orders to the pharmacy department, hospital staff should readily accept this mechanism.

  4. Email - In today's high-tech world, the use of electronic mail is commonplace. Email to the pharmacy department alerting of a suspected ADR is another alternative to allow hospital personnel to communicate with the pharmacy department.

  5. Make it Multidisciplinary - ADR reporting is not the sole responsibility of the pharmacy department. In order to be successful, a multidisciplinary approach is required. ADRs are not confined to the general medical floors. In any area of the institution where drugs are used, the potential for ADEs exists.

    Contact the respiratory therapy department and ask them to report ADRs associated with bronchodilators, such as albuterol-induced tachycardia, or ADRs associated with medications used in patients on ventilators, such as propofol-associated hypotension. Have the respiratory therapist report cases of acute respiratory depression secondary to medications that resulted in intubation of the patient. Contact the medical imaging department and ask them to report hypersensitivity reactions and renal dysfunction associated with contrast dye.

    Contact the endoscopy unit and determine how many patients experience ADRs associated with narcotic or benzodiazepine use. Institution-managed clinics are another area to look for ADRs. If the institution has an anticoagulation clinic, report warfarin-associated bleeds. The clinic probably already keeps track of this data for quality assurance purposes and may be willing to share it.

    Have the institution's heart clinic report ADRs associated with antihypertensives. Often, the pharmacy department does not venture into the sterile confines of the operating room (OR). If you have an OR satellite, you are one step closer to detecting ADRs in this area, because the pharmacist in the satellite should have developed a strong working relationship with the OR staff. ADRs that occur in the OR are associated with anesthetic agents, antibiotics used for surgical prophylaxis, analgesics, sedatives, and anxiolytics.

    Evaluate all admission diagnoses through the emergency department to look for drug-related illnesses such as gastrointestinal bleeds secondary to nonsteroidal anti-inflammatory agent use, acute hypersensitivity reactions to antibiotics, and acute acetaminophen overdoses.

  6. Look Outside the Institution's Walls - Look to primary care sites and walk-in clinics that are managed by the institution. If the institution's pharmacy department manages medication use at these sites, this is another area to look for ADRs.

  7. Provide Incentives - Motivate other departments to report ADRs by providing incentives such as a free lunch, a premier parking space, gift certificates, or movie passes. Challenge departments to see who reports more ADRs over a month's time. Compare the number of ADRs reported by various departments and recognize the department with the highest number of reports. Most departments are competitive and will rise to the challenge.

  8. Administrative Support - Get the support of top hospital officials, including the CEO, COO, and Director of Nursing. The reporting of ADRs must be a hospital priority that is funded and supported from the top down.

  9. Medical Staff Support - In order to get the support of physicians, they must be educated that reporting ADRs will not be punitive and will not be used for credentialing purposes. Obtain the support of the medical director. Physicians must be educated about the benefits of reporting ADRs and the impact such reporting will have on improving the quality of care of their patients. ADR event reporting can lead to changes in policies and procedures to control medications with a high potential for adverse effects. Surveillance of ADRs can result in educational programs for physicians and nurses designed to provide information to prescribe, administer, and monitor medications to minimize the risk of ADEs. Reporting of unique ADRs to the FDA can result in medication labeling changes that will benefit patients, such as the recent labeling changes mandated by the FDA for alosetron (Lotronex, Glaxo-Wellcome) due to reports of serious risk, including ischemic colitis. Such reports may also lead to the removal of medications from the market such as troglitazone (Rezulin, Warner-Lambert) and cisapride (Propulsid, Janssen). Report success stories at grand rounds, physician-attended committees, and in the pharmacy newsletter.

    The importance of reporting suspected ADRs to the FDA cannot be overstated. The FDA is responsible for conducting postmarketing surveillance of approved medications to identify ADRs that were not detected during premarketing review. The FDA receives approximately 275,000 ADR reports annually.[15] Premarketing trials frequently do not have sufficient power to reliably detect ADRs that may occur at rates of 1 in 10,000 or fewer drug exposures.[16]

    The FDA's Medical Products Reporting and Safety Information Program, MedWatch, is the mechanism whereby suspected ADEs are tracked and evaluated. The information reported enables the FDA to identify new ADRs not previously seen in clinical trials, update product package labeling to include new ADRs, disseminate relevant information to healthcare practitioners in the form of "Dear Doctor" letters, and in cases of severe ADRs, removal of the product from the market. However, in order for this program to be successful, the assistance of all involved in the healthcare system, including the patient, prescriber, nurse, pharmacist, and manufacturer, must report all suspected ADRs. Failure to do so delays identification of potentially predictable ADRs and puts countless patients at risk. To report a suspected ADR, contact the FDA via telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, or via Internet at http://www.fda.gov/medwatch. Additional information on the FDA's efforts to minimize the risk of preventable ADEs is available at, http://www.medscape.com/medscape/pharmacists/journal/2000/v01.n04/mph7174.phil/mph7174.phil-01.html.[15]

    The Institute for Safe Medication Practices is another source for reporting. This agency analyzes ADEs and develops and provides education about medication errors and ADRs.

  10. Target Antidote Medications - Have pharmacists screen orders for antidote medications. Examples of such medications are listed in Table 2. A physician order to discontinue antibiotics and administer an antihistamine is highly suggestive of an ADR and should be investigated.

    Classen and associates[17] described a computer system to detect ADRs from discontinuation orders, dosage decreases, antidote orders, and laboratory test orders. During the 18-month study period, the computerized system detected 731 ADRs in 36,653 patients, whereas the traditional voluntary detection methods identified only 9 reports. Dormann and colleagues[18] used a similar system to compare computerized monitoring of ADRs vs stimulated spontaneous reporting. Computer-based monitoring detected ADRs in 34 cases, whereas stimulated spontaneous reporting detected ADRs in 17 cases. The relative sensitivity of the computer-based monitoring was 74% (relative specificity, 75%) and that of stimulated spontaneous reporting was 37% (relative specificity, 98%). The authors concluded that computer monitoring is an effective method for improving the detection of ADRs.

  11. Use the Lab - The hospital laboratory is another department that can provide assistance in the detection of ADRs. Reports of patients with elevated aminoglycoside and vancomycin levels may reveal patients with drug-induced nephrotoxicity or drug-induced ototoxicity. Reports of toxic plasma concentrations of digoxin, theophylline, phenytoin, and lithium are other sources of ADRs. The microbiology laboratory can assist in the detection of antibiotic-associated diarrhea with a report of positive Clostridium difficile toxin assays. If the pharmacy computer system is interfaced with the laboratory system, more sophisticated ADR detection is possible; patients with elevated potassium levels receiving angiotensin-converting enzyme inhibitors can be used to pinpoint drug-induced hyperkalemia.

    Over 75% of all ADRs are dose related, occurring at standard, manufacturer-recommended doses.[19] These doses may be too high for some patients, resulting in toxic serum concentrations and adverse effects. Cohen describes one mechanism to prevent ADRs by identifying at-risk patients and initiating drug therapy with lower than manufacturer-recommended doses and gradually titrating the dosage up with careful monitoring.[19]

    Patient response can vary 4-fold to 40-fold with any drug at any given dose[20]; therefore, patient-specific doses are necessary to minimize dose-related side effects.

  12. Get Pharmacists out of the Pharmacy - By assigning a pharmacist to the nursing units, the detection of ADEs will be greatly enhanced. Many ADRs are considered "normal" reactions to medications and are not noteworthy enough to make it into the medical record. These are the types of reactions that are discussed on rounds but rarely documented, such as narcotic-induced constipation, antihistamine-induced sedation, and diuretic-induced electrolyte disturbances. Leape and associates[21] reported on the impact of pharmacist participation on physician rounds and ADEs in the intensive care unit and found the availability of a registered pharmacist on rounds was associated with a lower rate of ADEs. The rate of preventable ADEs decreased by 66% from 10.4 per 1000 patient-days (95% confidence interval, 7-14) to 3.5 (95% confidence interval, 1-5; P < .001).

    Limon[22] describes the role of the pharmacist in managing the risk vs benefit in the use of medication.

  13. Work With Medical Records - No one reads the medical record more thoroughly than the medical records coders. Work with them and have them contact the pharmacy department when they discover an ADR. A report of "E-codes" identifying an adverse occurrence is helpful to retrospectively detect ADEs. Although all E-codes are not related to medications, the majority are, and this is a simple method to help you uncover significant reactions.

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