Correspondence
Adverse Drug Events in Ambulatory Care
N Engl J Med 2003; 349:303-305July 17, 2003
- Article
To the Editor:
Gandhi and colleagues (April 17 issue)1 report that an adverse drug event occurred in 25 percent of outpatients who received at least one prescription during a four-week period. Establishing a cause–effect relation, however, represents the biggest problem in the analysis of drug-induced disease. To attribute an adverse event to a drug, there must be a plausible temporal relation to drug administration; in addition, the event must not be explainable by concurrent disease and must cease when the drug is discontinued and recur on a rechallenge that is conducted according to a satisfactory procedure. Otherwise, the cause–effect relation is only a probability.2 The descriptions of serious adverse drug events in the study by Gandhi et al. reveal only one case in which symptoms disappeared after the medication was discontinued. In the remaining patients, although the medication was discontinued, the outcome was not reported. As Tierney notes in the accompanying editorial,3 most of the adverse effects noted were nonspecific symptoms with a high prevalence in the general population that might sometimes be consequences of the concurrent disease. Thus, it would be important to have more information, including at least knowledge of the outcome of discontinuation of the drug.
3 ReferencesJesús Hernández, Ph.D.
M. Luisa Vargas, Ph.D.
University of Murcia, 30100 Murcia, Spain
jehernca@um.es 1
Gandhi TK ,Weingart SN ,Borus J , et al. Adverse drug events in ambulatory care. N Engl J Med 2003;348:1556-1564
Full Text | Web of Science | Medline2
Edwards IR ,Aronson JK . Adverse drug reactions: definition, diagnosis, and management. Lancet 2000;356:1255-1259
CrossRef | Web of Science | Medline3
Tierney WM . Adverse outpatient drug events -- a problem and an opportunity. N Engl J Med 2003;348:1587-1589
Full Text | Web of Science | Medline
To the Editor:
I was pleased to see that in Dr. Tierney's editorial regarding adverse events in outpatients, he included increased involvement of pharmacists as part of his potential solutions to this ongoing problem. Repeatedly, we see published reports of problems associated with the treatment of chronic diseases, including medication errors, adverse reactions, polypharmacy, undertreatment of pain, and lack of adherence to national guidelines. With the increasing demands placed on busy physicians, it is difficult for anyone to keep abreast of all the latest advances in medicine. Lack of time is the physician's biggest enemy. Continuing to tweak a failing system will not change the outcome. It is time for a fundamental change. It is time for the role of the pharmacist in direct patient care to increase substantially. There are well-trained, board-certified clinical pharmacists who are willing to accept the responsibility — and liability — of the pharmacologic management of chronic diseases. But it will take a legislative change in pharmacists' provider status and a willingness on the part of physicians to allow this to happen on a national scale.
Dennis Snow, Pharm.D.
Scottsdale Healthcare, Scottsdale, AZ 85260
dsnow@shc.org Author/Editor Response
In general, we concur with Drs. Hernández and Vargas regarding the importance of establishing cause–effect relations between medications and adverse drug events. In our observational study, however, we were unable to control the actions of participating physicians. Two independent physician reviewers adjudicated each candidate adverse drug event, using data on the type of symptoms, their timing, their frequency, and the plausibility of their relation to the drug in order to determine the credibility of the relation; these reviewers had good agreement. In addition, the patients' primary physicians agreed with the reviewers' conclusion about the relation between the drug and the symptoms in most cases (unpublished data). Given the limitations of observational studies, this method seemed reasonable.
The practice of discontinuing a medication and then rechallenging the patient with the same medication (“n-of-1” trials) could be much more widely used in practice to reduce the rate of ameliorable events.1 It is often difficult to tell whether a specific symptom was caused by a medication, and this approach can be helpful, especially in situations in which the therapeutic options are limited. Discontinuing and then restarting potentially beneficial medications to which the patient has had an equivocal reaction should be strongly considered by patients and their physicians as they make decisions about care.
1 ReferencesTejal K. Gandhi, M.D., M.P.H.
Brigham and Women's Hospital, Boston, MA 02115
tgandhi@partners.org Saul N. Weingart, M.D., Ph.D.
Beth Israel Deaconess Medical Center, Boston, MA 02215David W. Bates, M.D.
Brigham and Women's Hospital, Boston, MA 021151
Guyatt GH ,Keller JL ,Jaeschke R ,Rosenbloom D ,Adachi JD ,Newhouse MT . The n-of-1 randomized controlled trial: clinical usefulness: our three-year experience. Ann Intern Med 1990;112:293-299
Web of Science | Medline
Author/Editor Response
I agree that as the last health care professionals to see patients before they take medicines, pharmacists have a key role in pharmacotherapy. Because many patients have more than one doctor but usually visit a single pharmacy, pharmacists can enhance the continuity of care. I also agree that changing pharmacists' roles will require a fundamental transformation in the attitudes of the public, physicians, and pharmacists themselves.
However, we need a degree of healthy skepticism. My colleagues and I performed a randomized, controlled trial of a comprehensive pharmaceutical care program for 1113 patients with reactive airway disease who were receiving drugs from 36 community drugstores.1 Although we involved the pharmacists in developing the intervention,2 they seldom used the intervention materials, despite continued reinforcement and financial incentives. The intervention had no effect on clinical or patient-centered outcomes, and patients who were randomly assigned to receive “pharmaceutical care” from pharmacists had significantly more emergency department visits for acute respiratory disease than did control patients.
The new paradigm of team-oriented health care should include pharmacists if such inclusion would improve pharmacotherapy and reduce the rate of adverse drug events. However, this hypothesis should be rigorously tested.
2 ReferencesWilliam M. Tierney, M.D.
Indiana University School of Medicine, Indianapolis, IN 462021
Weinberger M ,Murray MD ,Marrero DG , et al. Effectiveness of pharmacist care for patients with reactive airways disease: a randomized, controlled trial. JAMA 2002;288:1594-1602
CrossRef | Web of Science | Medline2
Weinberger M ,Murray MD ,Marrero DG , et al. A pharmaceutical care program for patients with reactive airways disease. Am J Health Sys Pharm 2001;58:791-796
Web of Science | Medline
- Citing Articles (2)
Citing Articles
1
Kevin T. Fuji, Kimberly A. Galt. (2008) Pharmacists and Health Information Technology: Emerging Issues in Patient Safety. HEC Forum 20:3, 259-275
CrossRef2
C Andrew Brown, Jessica H. Bailey, Joshua Lee, Paula K. Garrett, William J. Rudman. (2006) The Pharmacist-Physician Relationship in the Detection of Ambulatory Medication Errors. The American Journal of the Medical Sciences 331:1, 22-24
CrossRef
