Pilot testing of checklists to discern adverse drug reactions and adverse drug events

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Tools for AdvAncing PhArmAcy PrAcTice

Abstract

Objectives: To estimate the prevalence of patient-reported adverse drug events (ADEs)/adverse drug reactions (ADRs) in the community pharmacy setting and determine the prevalence relative to pharmacist judgment.

Data sources: The 2009 version of the Pharmacy Times top 200 drugs was used to identify the prescription medications most commonly used within the ambulatory population during 2008. All ADEs/ADRs for each medica-tion were obtained by combining the ADEs/ADRs listed in Drug Facts and Comparisons, Lexi-Comp, and Micromedex.

Methods: Checklists for each pharmacologic class within the top 200 medi-cations (n = 51) were developed, with questions about the five most com-mon ADEs/ADRs in each class. Ten community pharmacies administered the checklists. Patients requesting a prescription refill for a medication listed in the top 200 were asked to complete a class-specific checklist to determine ADEs/ADRs experienced in the previous 4 weeks. Upon completion, phar-macists engaged in routine counseling procedures, including a discussion of patient-reported ADEs/ADRs. Pharmacists indicated if they believed, based on their clinical judgment, whether the ADE/ADR reported was re-lated to the medication.

Results: 2,057 checklists were completed, with a total of 10,285 poten-tial ADEs/ADRs. Patients reported 2,185 ADEs/ADRs (21.24%), with 755 (7.3%) definitively confirmed by the pharmacist as being related to their medication.

Conclusion: Use of these checklists resulted in the identification of previ-ously unrecognized ADEs/ADRs in the community setting. Routine use of these short, patient-completed checklists may assist pharmacists in earlier identification of ADEs/ADRs, which can have a positive impact on patient safety across settings.

Keywords: Adverse drug events, adverse drug reactions, pharmacy, phar-macists.

J Am Pharm Assoc. 2013;53:61–69.doi: 10.1331/JAPhA.2013.11196

Pilot testing of checklists to discern adverse drug reactions and adverse drug eventsAleda m.h. chen, mary e. Kiersma, Brian m. shepler, and matthew m. murawski

Received October 20, 2011, and in revised form January 31, 2012. Accepted for publi-cation January 31, 2012.

Aleda M.H. Chen, PharmD, MS, PhD, was doctoral candidate in the Department of Pharmacy Practice, College of Pharmacy, Purdue University, West Lafayette, IN, at the time this study was conducted; she is currently Assistant Professor, School of Pharmacy, Cedarville University, Cedar-ville, OH. Mary E. Kiersma, PharmD, MS, PhD, is Director of Assessment and As-sistant Professor, College of Pharmacy, Manchester College, Fort Wayne, IN. Brian M. Shepler, PharmD, is Clinical Associate Professor and Director of Advanced Phar-macy Practice Experiences; and Matthew M. Murawski, BSPharm, PhD, is Associate Professor of Pharmacy Administration, Col-lege of Pharmacy, Purdue University, West Lafayette, IN.

Correspondence: Matthew M. Murawski, BSPharm, PhD, College of Pharmacy, Pur-due University, 575 Stadium Mall Dr., West Lafayette, IN 47907-2051. Fax: 765-496-1886. E-mail: [email protected]

Disclosure: Dr. Chen and the Purdue Uni-versity Center on Aging and the Life Course were supported by grant T32AG025671 from the National Institute on Aging, Na-tional Institutes of Health. Dr. Murawski was supported by a Lilly Endowment seed grant awarded through the College of Pharmacy, Purdue University. The other authors de-clare no conflicts of interest or financial in-terests in any product or service mentioned in this article, including grants, employment, gifts, stock holdings, or honoraria.

Previous presentation: American Phar-macists Association Annual Meeting & Ex-position, Seattle, WA, March 25–28, 2011.

Downloaded From: http://www.japha.org/ by Aleda Chen on 03/06/2013

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Tools ADR/ADE CHECkLIST PILOT TESTING

ADEs/ADRs.13 Previous research has demonstrated pharmacists’ ability to reduce the incidence of ADEs in hospital and community settings but in hospital settings primarily.14–24 The need to monitor patients in the am-bulatory population for ADEs/ADRs is considerable. Given the demonstrated ability of pharmacists to pre-vent, address, and resolve ADEs/ADRs in the hospital setting,14–24 pharmacists practicing in the community set-ting also are capable of performing the same tasks with regard to ADEs/ADRs. Counseling in the community setting has been found to reduce ADEs in cardiovascu-lar patients21 and with nonsteroidal anti-inflammatory drug use.25 Because community pharmacists are highly accessible to patients, they are uniquely positioned in the health care system to address the issue of ongoing ADEs/ADRs in ambulatory patients and prevent seri-ous outcomes.

The time constraints of modern practice may limit community pharmacists’ opportunities to identify ADEs/ADRs, as pharmacists spent as much as 72% of their time in medication dispensing and managerial ac-tivities.26 Tools such as TIMER (Tool to Improve Medica-tions in the Elderly via Review) have been used during medication therapy management in the community set-ting to successfully aid pharmacists in identifying drug-related problems.27 Other tools used in the community setting have been aimed at identifying inappropriate medications among older adult patients.28 However, de-veloping short pharmaceutical class–specific checklists based on common ADEs/ADRs that a patient might ex-perience may allow busy community pharmacists to not only more efficiently identify whether an ADE/ADR is occurring and the causative agent but also assist other health care providers in optimizing medication therapy for patients. Routine administration of these medica-tion-specific checklists could aid in earlier identification of ADEs/ADRs, especially in the ambulatory care set-ting, thereby improving patient safety and outcomes. These checklists also can assist in more accurate iden-tification of the prevalence of ADEs/ADRs for specific medications.

objectivesWe sought to (1) estimate the prevalence of patient-reported ADEs/ADRs in the community pharmacy setting and (2) determine the incidence/prevalence of ADEs/ADRs relative to pharmacists’ expert judgment.

methodsChecklists for each pharmacological class were devel-oped and contained questions regarding the five most common ADEs/ADRs in each class. Only the five most common ADEs/ADRs were used to keep the checklists brief and feasible for use in a busy community phar-macy. As described previously in greater detail, the five most common ADEs/ADRs within the class were iden-

At a GlanceSynopsis: Pharmacist administration of short, five-item checklists for the top 200 prescription medications in the community pharmacy set-ting resulted in the identification of adverse drug events (ADEs)/adverse drug reactions (ADRs). Patients reported 2,185 ADEs/ADRs, 755 of which were confirmed by pharmacists as being related to patients’ medications. Short checklists can assist pharmacists in identifying and addressing ADEs/ADRs in the community setting, which may pro-vide a better understanding of the incidence and prevalence of ADEs/ADRs.

Analysis: Similar to previous research, this study found that adrenal corticosteroids, antidepressants, anticonvulsants, antihypertensives, and cardiovascu-lar agents had high incidence rates of patient-reported ADEs/ADRs. A need exists for earlier identification of ADEs/ADRs in the ambulatory care setting, and com-munity pharmacists are well positioned to assist in this important patient safety measure. Developing short checklists based on common ADEs/ADRs that patients might experience may allow busy community pharma-cists to identify whether an ADE/ADR is occurring and determine the causative agent, as well as assist other health care providers in optimizing medication therapy for patients.

In recent decades, the amount of medications con-sumed and the spending on prescription drugs has

increased markedly, as more than 80% of adults older than 56 years take at least one prescription medication daily.1,2 The concurrent rise in the number of prescrip-tions also has led to an increase in adverse drug events (ADEs) and adverse drug reactions (ADRs). An ADR is typically defined as “harm directly caused by a drug at normal doses,”3 while an ADE is “harm caused by the use of a drug.”3 According to the Food and Drug Admin-istration, although serious and fatal ADEs more than doubled from 1998 to 2005,4 ADEs/ADRs overall may be underreported by as much as 94%.5–7 The reported average annual prevalence of provider-reported ADEs/ADRs across community and hospital settings has been estimated at 0.5%.8 The outcomes of ADEs/ADRs can be severe and costly. Patients presenting to the emergency department with an ADE/ADR have a higher risk of longer hospital stays, more outpatient visits, and nearly double the cost of care of those without ADEs/ADRs.9 ADEs/ADRs result in at least 100,000 deaths yearly, and the costs associated with ADE/ADR-related morbidity and mortality are greater than $177 billion.10–12

Pharmacists are well prepared to address and re-solve medication-related problems that patients expe-rience and can provide important information about



ADR/ADE CHECkLIST PILOT TESTING Tools

tified through an extensive literature review.29 In brief, the 2009 version of the Pharmacy Times top 200 drugs (by prescription volume) list was used to identify the pre-scription medications most commonly used within the ambulatory population during 2008.30 All ADEs/ADRs for each medication were obtained from Drug Facts and Comparisons, Lexi-Comp, and Micromedex during July to November 2009. All three databases were used to develop the comprehensive list and to ensure complete-ness. Each medication was categorized and sorted ac-cording to pharmacological class (n = 51). To determine which ADEs/ADRs were the most common within a pharmacologic class, all ADEs/ADRs for each medica-tion within the class were listed. Estimates of frequency of ADE/ADR occurrence and frequency versus placebo, when available, also were obtained. After this list was compiled, the frequency of adverse effects was added for all medications within the pharmacologic class to represent the rate of incidence. This method was used to provide greater weight to adverse effects that occur for a larger proportion of the medications within a par-ticular class. The top five highest percentages were used as the five most common ADEs/ADRs for a particular class. The Micromedex database also lists the most com-mon adverse effects for each pharmacologic class; there-fore, if a particular class did not have any information regarding the frequency of ADEs/ADRs, the list of most common adverse effects in the Micromedex database was used to determine the five most common adverse effects.29

For example, muscle pain was listed as an ADE/ADR for all medications (pravastatin, ezetimibe/sim-vastatin, rosuvastatin, fenofibrate, ezetimibe, simv-astatin, and atorvastatin) represented within the anti-dyslipidemic agent category. The frequency of muscle pain occurrence for each medication was added to pro-vide a cumulative percentage of 37%. After performing this procedure for each of the adverse effects within the antidyslipidemic agent category, muscle pain was found to be among the five most common ADEs/ADRs in the class.

After the five most common ADEs/ADRs within a class were determined, an extensive review of the lit-erature for each pharmacologic class, medication, and ADE/ADR was conducted. Several steps were used in the literature review and question development. Using Medline, a literature review for each of the 51 pharma-cological classes, the medications within each class, and the ADEs/ADRs within each class was performed to determine the different methods whereby patients de-scribe common ADEs/ADRs. For example, when fram-ing the question for antidyslipidemic agents related to muscle pain, the literature was searched by class and by medication within the class to determine the different ways patients and providers referred to and measured “muscle pain.” Another search then was completed

with those terms identified, such as “myalgia,” to en-sure completeness of the literature review. Any publicly available valid and reliable instruments that referred to the ADEs/ADRs being evaluated also were examined during this process.

Using the information gathered from the extensive literature review, questions were developed regarding the occurrence of particular ADE/ADR within the pre-vious 4 weeks. The time frame of 4 weeks was selected for two reasons: (1) medications in the community set-ting are typically filled for a 30-day supply and (2) pre-vious research has demonstrated that a 4-week recall is comparable in accuracy with shorter recall periods, such as 1 week.31 The questions then were turned into check-lists for each pharmacologic class, representing the five most common ADEs/ADRs.

After the checklists were developed, Purdue Uni-versity Institutional Review Board approval was ob-tained. A convenience sample of 10 community phar-macy sites throughout the state of Indiana were identi-fied and recruited for this study. To be as representative as possible of community pharmacy practice in Indiana, the community pharmacies selected included rural and urban locations, low- and high-volume stores, and in-dependent and chain pharmacies. Each of the 10 sites were asked to approach patients currently refilling a prescription represented in the top 200 medication list (Table 1) and invited to participate. While waiting for their prescription to be refilled, participants were asked to complete the pharmacologic class–specific checklist for their prescription medication. For example, if a pa-tient was refilling a prescription for simvastatin, the pa-tient would complete the checklist for antidyslipidemic agents.

On the checklist, patients indicated whether they had experienced any of the five most common adverse effects in the previous 4 weeks by checking “yes” or “no.” The pharmacists were instructed to review com-pleted checklists before counseling patients on their pre-scriptions. The pharmacists followed normal counseling procedures and counseled patients on their medications and indicated ADEs/ADRs. After counseling, the phar-macists were instructed to check a box to the right of the question to indicate, based on their clinical professional judgment, whether the ADE/ADR occurrence noted by the patient was likely a consequence of the patient’s medication.

Data analysisPASW software for Windows (version 18.0; SPSS, Chi-cago) was used for analysis. Double entry of all data occurred to identify keystroke errors. An a priori level of 0.05 was used for statistical significance. Descriptive statistics were used to determine the incidence of spe-cific ADEs/ADRs within each pharmacologic class and across all 51 classes because certain adverse effects, such




Table 1. Top 200 medications and pharmacologic category

Pharmacologic category Top 200 medicationsAdrenocortical steroid PrednisoneAgent for gout AllopurinolAminopenicillin Amoxicillin, amoxicillin TR/clavulanate potassiumAngiotensin-converting enzyme inhibitor Enalapril maleate, lisinopril, ramiprilAngiotensin II receptor antagonist Irbesartan (Avapro), olmesartan (Benicar), losartan (Cozaar), valsartan (Diovan)Antiadrenergic agent ClonidineAnticholinergic Ipatropium bromide/albuterol sulfate (Combivent), tolterodine tartrate (Detrol LA), tiotropium bromide

(Spiriva Handihaler)Anticoagulant Warfarin sodiumAnticonvulsant Valproic acid (Depakote ER), gabapentin (Neurontin), lamotrigine (Lamictal), pregabalin (Lyrica), topira-

mate (Topamax)Antidepressant

Amitriptyline hydrochloride, bupropion (Budeprion XL), citalopram hydrochloride, duloxetine (Cymbalta), venlafaxine (Effexor XR), fluoxetine hydrochloride, escitalopram (Lexapro), paroxetine hydrochloride, ser-traline hydrochloride, trazodone hydrochloride

Antidiabetic agent Pioglitazone (Actos), glyburide, sitagliptin phosphate (Januvia), insulin glargine (Lantus), metformin hy-drochloride

Antidopaminergic Promethazine hydrochlorideAntifungal (triazole) FluconazoleAntihistamine Fexofenadine hydrochlorideAntidyslipidemic agent Rosuvastatin (Crestor), atorvastatin calcium (Lipitor), pravastatin sodium, fenofibrate (Tricor), simvastatin,

ezetimibe/simvastatin (Vytorin), ezetimibe (Zetia)Antihypertensive combinations Amlodipine besylate/benazepril, olmesartan/hydrochlorothiazide (Benicar HCT), valsartan/hydrochloro-

thiazide (Diovan HCT), losartan/hydrochlorothiazide (Hyzaar), lisinopril/hydrochlorothiazideAnti-infective agent Moxifloxacin (Avelox), azithromycin, cephalexin, ciprofloxacin hydrochloride, doxycycline hyclate, levo-

floxacin (Levaquin), penicillin VK, sulfamethoxazole/trimethoprim, valacyclovir hydrochloride (Valtrex)Antiplatelet agent Clopidogrel (Plavix)Antipsychotic agent Aripirazole (Abilify), risperidone (Risperdal), quetiapine (Seroquel), olanzapine (Zyprexa)Benzodiazepine Alprazolam, clonazepam, diazepam, lorazepamBisphosphonate Risendronate (Actonel), alendronate sodium, ibandronate (Boniva)Bronchodilator Albuterol (ProAir HFA, Proventil HFA)Calcium channel blocker Amlodipine besylate, diltiazem (Cartia XT), verapamil SRCardiovascular agent Atenolol, digoxin, tamulosin hydrochloride (Flomax), metoprolol succinate, metoprolol tartrate, metoprolol

succinate (Toprol XR)Cholinesterase inhibitor Donepezil (Aricept)CNS stimulant Dextroamphetamine/amphetamine (Adderall XR), methylphenidate (Concerta)Contraceptive hormone

Etonogestrel/ethinyl estradiol (NuvaRing), norgestimate/ethinyl estradiol (Ortho Tri-Cyclen Lo), norgesti-mate/ethinyl estradiol (Trinessa-28), ethinyl estradiol/drospirenone (Yasmin 28), ethinyl estradiol/drospi-renone/levonorgestrel (Yaz-28)

Dermatological agent Lidocaine hydrochloride (Lidoderm)Diuretic Furosemide, hydrochlorothiazide, triamterene/hydrochlorothiazideElectrolyte Potassium chloride (Klor-Con M20), potassium chlorideEstrogens Conjugated estrogens (Premarin)Gastrointestinal agent Ranitidine hydrochlorideImpotence agent Tadalafil (Cialis), sildenafil citrate (Viagra)Intranasal steroid Fluticasone propionateLeukotriene receptor antagonist Monteleukast (Singulair)Narcotic analgesic Propoxyphene napsylate/acetaminophenNMDA receptor antagonist Memantine hydrochloride (Namenda)Nonsteroidal anti-inflammatory agent Celecoxib (Celebrex), ibuprofen, meloxicam, naproxenNutrient/nutritional agent Folic acid, nicotinic acid (Niaspan), vitamin D




as nausea, occurred in more than one pharmacologic class. For example, we tallied the incidence of nausea within each pharmacologic class and across the entire sample of all pharmacologic classes. ADEs/ADRs were ranked by incidence within each pharmacologic class and across the entire sample.

The incidence of ADEs/ADRs then were compared with the pharmacist-generated data regarding the phar-macist’s judgment regarding whether reported ADEs/ADRs were in fact drug-related using a chi-square anal-ysis. The results were analyzed to determine the level of correspondence between patient report and pharmacist judgment for each ADE/ADR reported, for each phar-macologic class, and across all 51 pharmacologic classes.

resultsA total of 2,057 checklists were completed by patients across 10 pharmacy study sites from August 2010 to June 2011. The five classes with the most completed surveys were antidyslipidemic agents (n = 99), angiotensin-con-verting enzyme inhibitors (n = 89), antidiabetic agents (n = 78), antidepressants (n = 77), and diuretics (n = 75). The five classes with the least completed surveys were cho-linesterase inhibitors (n = 8), dermatological agents (n = 8), NMDA (N-methyl-D-aspartate) receptor antagonists (n = 8), selective estrogen receptor modulators (n = 6), and serotonin 5-HT1 receptor agonists (n = 5) (Table 2).

A total of 10,285 possible ADEs/ADRs were listed on the 2,057 checklists (5 ADEs/ADRs per checklist) completed. The incidence rate within possible patient-reported ADEs/ADRs was 21.24% (n = 2,185 of 10,285). Of those 2,185 patient-reported ADEs/ADRs, nearly 35% had pharmacist agreement that the ADE/ADR oc-currence was a likely consequence of the particular med-ication. Approximately 56% of patient-reported ADEs/ADRs had no indication of agreement or disagreement by the pharmacist. Pharmacists indicated that the re-maining 5% of patient-reported ADEs/ADRs were not caused by the particular medication (Table 3).

Some pharmacologic classes had high rates of pa-tients reporting at least one ADE/ADR of the possible five ADEs/ADRs per checklist. Cardiovascular agents (75%), antidepressants (73%), antidopaminergics (68%), opioid analgesics (65%), anticholinergics (64%), and anticonvulsants (64%) had the highest rates of patients who reported at least one ADE/ADR (Table 2). Other classes, such as serotonin 5-HT1 receptor modulators (20%), agents for gout (22%), and bisphosphonates (26%), had the lowest rates of patients who reported at least one ADE/ADR.

Because patients could report more than one ADE/ADR per pharmacologic class, several pharmacologic classes had the most overall patient-reported ADEs/ADRs (Table 4). Across all patients, nearly 50% of pa-tients reported at least one ADE/ADR. The top five classes with the most patient-reported ADEs/ADRs (of possible listed ADEs/ADRs) were antidepressants (35%), cardiovascular agents (34%), anticonvulsants (33%), adrenocortical steroids (30%), and antiadrenergic agents (28%). The classes with the fewest patient-report-ed ADEs/ADRs were agents for gout (9%), antifungals (10%), leukotriene receptor antagonists (11%), gastroin-testinal agents (11%), and estrogens (11%).

Overall, 34% of patient-reported ADEs/ADRs were verified by pharmacists as likely consequences of par-ticular medications. The top five classes with the high-est level of patient–pharmacist congruence were adrenal corticosteroids (23%), antidopaminergics (21%), smok-ing deterrents (18%), nutrient/nutritional agents (17%), and antipsychotics (16%) (Table 5).

discussionAdministering five-item checklists for the top 200 pre-scription medications to patients refilling medications at a community pharmacy resulted in a high incidence of patient self-report of ADEs/ADRs. Among patients, 49.64% reported at least one ADE/ADR; across all pos-sible ADEs/ADRs, the overall incidence rate was 2,185

Table 1 continuedOpioid analgesic Oxycodone hydrochloride (OxyContin), tramadol hydrochlorideOpioid analgesic combination Acetaminophen/codeine, hydrocodone/acetaminophen, oxycodone/acetaminophenProstaglandin antagonist Latanoprost (Xalatan)Proton pump inhibitor Rabeprazole (Aciphex), esomeprazole (Nexium), omeprazole, pantoprazole sodium, lansoprazole (Prevacid)Respiratory agent Fluticasone proprionate/salmeterol (Advair Diskus, fluticasone propionate (Flovent HFA), mometasone

furoate monohydrate (Nasonex)Sedatives/hypnotics Zolpidem tartrate (Ambien CR), eszopiclone (Lunesta), zolpidem tartrateSelective estrogen receptor modulator Raloxifene (Evista)Serotonin 5-HT1 receptor agonist Sumatriptan succinate (Imitrex)Skeletal muscle relaxant (centrally acting) Carisoprodol, cyclobenazaprine hydrochlorideSmoking deterrent Varenicline tartrate (Chantix)Thyroid hormones Levothyroxine sodium, levothyroxine (Levoxyl), levothyroxine sodium (Synthroid)Vasodilator (nitrate) Isosorbide mononitrateAbbreviations used: CNS, central nervous system; HT, hydroxytryptamine; NMDA, N-methyl-D-aspartate.




Table 2. Overall Incidence of ADEs/ADRs by pharmacologic class

Pharmacologic categoryCompleted surveys

Reported at least one ADE/ADR No. (%)

Total possible ADEs/ADRs

Total ADEs/ADRs reported No. (%)

Adrenocortical steroid 34 20 (58.82) 170 51 (30.00)Agent for gout 37 8 (21.62) 185 17 (9.19)Aminopenicillin 30 14 (46.67) 150 22 (14.67)Angiotensin-converting enzyme inhibitor 89 39 (43.82) 445 78 (17.53)Angiotensin II receptor antagonist 57 23 (40.35) 285 48 (16.84)Antiadrenergic agent 34 18 (52.94) 170 48 (28.24)Anticholinergic 39 25 (64.10) 195 47 (24.10)Anticoagulant 45 19 (42.22) 225 44 (19.56)Anticonvulsant 39 25 (64.10) 195 64 (32.82)Antidepressant 77 56 (72.73) 385 133 (34.55)Antidiabetic agent 78 46 (58.97) 390 96 (24.62)Antidopaminergic 25 17 (68.00) 125 35 (28.00)Antifungal (triazole) 26 9 (34.62) 130 13 (10.00)Antihistamine 36 16 (44.44) 180 26 (14.44)Antidyslipidemic agent 99 50 (50.51) 495 99 (20.00)Antihypertensive combinations 53 24 (45.28) 265 41 (15.47)Anti-infective agent 41 23 (56.10) 205 48 (23.41)Antiplatelet agent 47 23 (48.94) 235 58 (24.68)Antipsychotic agent 32 19 (59.38) 160 43 (26.88)Benzodiazepine 63 30 (47.62) 315 74 (23.49)Bisphosphonate 34 9 (26.47) 170 15 (8.82)Bronchodilator 22 11 (50.00) 110 17 (15.45)Calcium channel blocker 47 24 (51.06) 235 52 (22.13)Cardiovascular agent 68 51 (75.00) 340 116 (34.12)Cholinesterase inhibitor 8 5 (62.50) 40 8 (20.00)CNS stimulant 44 28 (63.64) 220 52 (23.64)Contraceptive hormone 60 36 (60.00) 300 59 (19.67)Dermatological agent 8 3 (37.50) 40 7 (17.50)Diuretic 75 30 (40.00) 375 64 (17.07)Electrolyte 42 15 (35.71) 210 33 (15.71)Estrogens 36 12 (33.33) 180 20 (11.11)Gastrointestinal agent 28 10 (35.71) 140 16 (11.43)Impotence agent 31 12 (38.71) 155 18 (11.61)Intranasal steroid 31 17 (54.84) 155 42 (27.10)Leukotriene receptor antagonist 35 11 (31.43) 175 20 (11.43)Narcotic analgesic 22 9 (40.91) 110 17 (15.45)NMDA receptor antagonist 8 5 (62.50) 40 9 (22.50)Nonsteroidal anti-inflammatory agent 38 17 (44.74) 190 35 (18.42)Nutrient/nutritional agent 36 18 (50.00) 180 38 (21.11)Opioid analgesic 31 20 (64.52) 155 39 (25.16)Opioid analgesic combination 60 21 (35.00) 300 38 (12.67)Prostaglandin antagonist 15 8 (53.33) 75 14 (18.67)Proton pump inhibitor 65 34 (52.31) 325 68 (20.92)Respiratory agent 36 14 (38.89) 180 25 (13.89)Sedatives/hypnotics 46 26 (56.52) 230 42 (18.26)Selective estrogen receptor modulator 6 2 (33.33) 30 4 (13.33)Serotonin 5-HT1 receptor agonist 5 1 (20.00) 25 3 (12.00)Skeletal muscle relaxant (centrally acting) 28 16 (57.14) 140 31 (22.14)




of 10,285 (21.24%). After examining pharmacist agree-ment regarding ADEs/ADRs, there was an ADE/ADR incidence rate of 755 (34.55%) that patients were most likely experiencing as a consequence of particular medi-cations.

Recent work has identified the need for earlier identification of ADEs/ADRs in the ambulatory care setting.8 Because patients visit pharmacies on a regular basis, community pharmacists are well positioned to as-sist in earlier identification of ADEs/ADRs. This project was designed to determine the feasibility of a system to assist community pharmacists in achieving this goal. However, few studies have previously examined the in-cidence rate of ADEs/ADRs in the community setting or used a similar approach to identifying ADEs/ADRs. Researchers have found estimated incidence rates of 123,000 ADEs/ADRs per year in France.32 In the United States, estimates vary from 50.1 ADEs/ADRs per 1,000 person-years among older adults,33 to 5.5 ADEs/ADRs per 100 patients,34 and to 7.70 visits per 1,000 persons.35 These studies identified and examined the incidence of serious ADEs/ADRs through the use of insurance claims, national surveys of ambulatory care, and cohort studies using data from physician records and hospital records.32–35 No literature was found describing the inci-dence of less serious, marginally tolerable ADEs/ADRs. Because few comparable studies exist, future work should validate the results of the current work.

Similar to the top 30 medications suspected to cause ADRs described by Kane-Gill et al.8 in their examination of an administrative database of 20 million patients, ad-renal corticosteroids, antidepressants, anticonvulsants, antihypertensives, and cardiovascular agents were found to have high incidence rates of patient-reported ADEs/ADRs. Further, adrenal corticosteroids, antido-paminergics, and antipsychotics, which had the great-est patient–pharmacist congruence in the current study, also were consistent with the results of Kane-Gill et al. Other studies support the results and provide evidence concerning specific medications and high ADE/ADR incidence rate.31

limitationsBecause this was a pilot study to examine the feasibility of these checklists, the validity of the checklists could not be examined. This study used pharmacies in Indiana; therefore, the results may not be generalizable to other states. Nearly 56% of ADEs/ADRs reported by patients

Table 2 continued

Smoking deterrent 20 9 (45.00) 100 23 (23.00)Thyroid hormones 70 34 (48.57) 350 65 (18.57)Vasodilator (nitrate) 21 9 (42.86) 105 18 (17.14)Total 2,057 1,021 (49.64) 10,285 2,093 (20.35)Abbreviations used: ADE, adverse drug event; ADR, adverse drug reaction; CNS, central nervous system; HT, hydroxytryptamine; NMDA, N-methyl-D-aspartate.

Table 3. Overall incidence of ADEs/ADRs

ADE/ADR reports No. (%)No reported ADEs/ADRs 8,145 (79.19)ADE/ADR reported

Pharmacist did not indicate agreement or disagree-ment 1,221 (11.87)Pharmacist indicated agreement 755 (7.34)Pharmacist indicated disagreement 117 (1.14)Missing 47 (0.45)Total 10,285

Abbreviations used: ADE, adverse drug event; ADR, adverse drug reaction.

Table 4. Pharmacologic classes with the most and least patient-reported ADEs/ADRs

Rank Pharmacologic class No. (%)1 Antidepressant 133 (34.55)2 Cardiovascular agent 116 (34.12)3 Anticonvulsant 64 (32.82)4 Adrenocortical steroid 51 (30.00)5 Antiadrenergic agent 48 (28.24)46 Leukotriene receptor antagonist 20 (11.43)46 Gastrointestinal agent 16 (11.43)48 Estrogens 20 (11.10)49 Antifungal (triazole) 13 (10.00)50 Agent for gout 17 (9.19)51 Bisphosphonate 15 (8.82)Abbreviations used: ADE, adverse drug event; ADR, adverse drug reaction.

Table 5. Pharmacologic classes with the highest level of patient–pharmacist congruence

Rank Pharmacologic class No. (%)1 Adrenal corticosteroid 39 (22.94)2 Antidopaminergic 26 (20.80)3 Smoking deterrent 18 (18.00)4 Nutrient/nutritional agent 31 (17.22)5 Antipsychotic 26 (16.25)6 CNS stimulant 34 (15.45)7 Intranasal steroid 21 (13.55)8 Selective estrogen receptor modulator 4 (13.33)9 Vasodilator 13 (12.38)10 Skeletal muscle relaxant 17 (12.14)Abbreviation used: CNS, central nervous system.




did not result in an indication of agreement or disagree-ment by the pharmacist regarding whether they were a likely consequence of the particular medication. This result is attributed to a shortcoming in the experimental design. Despite the low level of pharmacist response, 755 ADEs/ADRs were identified as a likely consequence of the medication. The experimental design was faulty be-cause it only asked pharmacists to indicate with a check if they agreed with patients’ self-report. No clear provi-sion was made to distinguish disagreement or failure to assess agreement with patient self-report. As a conse-quence, we were unable to differentiate false negatives (i.e., pharmacist did not bother or have to time to check agreement with patient box) from true negatives (i.e., pharmacist did not agree with patient report). There-fore, the reported rate of concordance between patient self-report and pharmacist expert judgment (34.55%) is the lower bound of concordance. Further research that details pharmacist input for each reported ADE/ADR will be required before the actual level of concordance between pharmacist judgment and patient report can be reliably established. Future research should refine the experimental design to more thoroughly explore pa-tient–pharmacist congruence, allow for further valida-tion of the system by comparison with other variables, assess the system’s usefulness in reducing ADEs/ADRs or improve patient outcomes, and examine the check-lists in other geographic regions.

conclusionAdministering short checklists to patients in the com-munity pharmacy setting for the top 200 prescription medications resulted in the identification of ADEs/ADRs. These checklists may assist pharmacists in iden-tifying and addressing ADEs/ADRs in the community setting, which may provide a better understanding of the incidence and prevalence of ADEs/ADRs. Phar-macist identification and resolution of patient-reported ADEs/ADRs is an important component of pharmaceu-tical care, materially enhancing patient quality of life. Use of these checklists shows promise for that purpose. ADEs/ADRs continue to be prevalent in the community setting, and future work should continue to determine ways to assist health care providers in identifying and resolving ADEs/ADRs.

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Florence Bridge • Florence, Italy • September 19, 2009 • Jack Beaucaire, BSPharm, MS


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Pilot testing of checklists to discern adverse drug reactions and adverse drug events