Ambulatory Medication Safety in Primary Care: A Systematic Review

Richard A. Young; Kimberly G. Fulda; Anna Espinoza; Ayse P. Gurses; Zachary N. Hendrix; Timothy Kenny; Yan Xiao

doi:10.3122/jabfm.2022.03.210334

Article Figures & Data

Tables

Figures

View popup

Table 1.

Noninterventional Studies

Lead Author (Year)	Setting	Number of Patients or Prescriptions	High-Risk Subpopulation?	Definition of Medical Error	Error Rate	Other Outcomes
Abramson¹⁵ (2011)	PC in NY	2432 paper prescriptions at baseline and 2079 electronic at 1 year	No	PIP—IOM definition of prescribing errors	16.0%
Abramson¹⁶ (2012)	PC in NY	1629 prescriptions at 3 months postimplementation, 1738 at 1 year	No	PIP—IOM definition of prescribing errors	4.5%
Al-Busadi¹⁷(2020)	Oman PC	377 patients	Ages 65+	PIP—Beers, STOPP	12.7%-17.2%
Almeida¹⁸ (2019)	Brazilian PC	227 patients	≥ 60 years of age	PIP—Beers	53.7%-63.4%
Amos¹⁹ (2015)	Italy PC	865,354 patients	Ages 65+	PIP—own definition (Maio)	28% had at least one PIP	8%, 10%, and 14% of individuals were prescribed at least one medication that “should always be avoided,” is “rarely appropriate,” and has “some indications but [is] often misused,” respectively.
Aspinall²⁰ (2002)	Pennsylvania Veterans Affairs PC	198 patient/provider pairs	No, but limited to a VA outpatient population	ADE—provider or patient report	26%	83 ADEs reported in active surveillance versus 1 in passive reporting
Aubert²¹ (2016)	Swiss university PC	1002 patients	Ages 50-80	PIP—STOPP PPO—START	PIP 6.7%, PPO 27.5%	> 65 years, 5.6% PIP, 32.2% PPO
Avery²² (2013)	England PC	6048 prescriptions for 1777 patients	No	PIP—own definition	4.9%
Awad²³ (2019)	Kuwait PC	478 patients, 2645 prescriptions	Ages 65+	PIP—Beers, STOPP, FORTA, MAI	44.3%-53.1%
Barry²⁴ (2016)	Northern Ireland PC	6826 patients	Medicine for dementia dispensed	PIP—STOPP	64.4%
Ble²⁵ (2015)	UK PC	13,900 patients	Ages 65+	PIP—Beers	38.4% any, 17.4% long-term
Bregnhoj²⁶ (2007)	Danish GP patients	212 patients, 1621 prescriptions	Age of 65+, taking 5 or medications	PIP—MAI	94.3%
Brekke²⁷ (2008)	Norwegian GP patients	85,836 patients	Ages 70+	PIP—own definition	18.4%
Bruin-Huisman²⁸ (2017)	Dutch GP patients	4537 patients per year	Ages 65+	PIP—STOPP PPO—START	34.7% PIP, 84.8% PPO
Cahir²⁹ (2014)	Irish PC	931 patients	Ages 70+	PIP—STOPP	42% PIP	Patients with ≥ 2 PIP indicators were twice as likely to have an ADE (adjusted OR 2.21), have a significantly lower mean HRQoL utility (adjusted coefficient −0.09), and nearly a 2‐fold increased risk in the expected rate of A&E visits (adjusted IRR 1.85).
Castillo-Paramo³⁰ (2014)	Spanish PC	272 patients	Ages 65+	PIP—STOPP PPO—START	37.5%-50.7%
Chen³¹ (2005)	England PC	37,940 patients	No	PIP—own definition	0.19% drug-drug, 0.49% drug-disease	Two thirds of PIP medications on PC medication list were started by hospital doctors
Clark³² (2007)	Scotland PC	2513 ADR reports in year 2000 and 1455 ADR reports in 2001	No	ADE—own definition	The “top 10” medications accounted for 1715 of 2817 (60.9%, 95% CI 59.1, 62.7) ADE reports but only 2.2 million out of a total of 128 million primary care prescriptions (1.7%).
Corona-Rojo³³ (2009)	Mexico public health centers	1400 patients	Ages 70+	PIP—own definition	53%
Dhabali³⁴ (2011)	Malaysia University PC	17,288 patients	No	PIP—own definition	5.3%
Dhabali³⁵ (2012)	Malaysia University PC	23,733 patients	No	PIP—own definition	0.87%
Diaz Hernandez³⁶ (2018)	US federally funded PC	2218 patients	Ages 65 + with at least one chronic condition who received pharmacy services with 2 or more medications and experienced a medication error or an ADE	Potential ADE and ADE—own definition, several sources	Medication errors 12.5/100, potential ADE 9.4/100, ADE 5.0/100
Doubova Dubova³⁷ (2007)	Mexico PC	624 patients	Ages 50+ with nonmalignant pain syndrome who received prescriptions of nonopioid analgesics	PIP—own definition	80%
Fiss³⁸ (2011)	German PC	744 patients	Ages 50+ who regularly took one or more drugs, rural areas of Germany, GP home visits	PIP—Beers	18%
Gnadinger³⁹ (2017)	Switzerland PC	197 cases of medication incidents 180 physicians (GP and pediatricians) at 144 practices	No	“Medication incidents” self-described	2.07 per GP per year = 46.5 per 100,000 contacts.
Goren⁴⁰ (2017)	Turkish PC	1206 patients	Ages 65+	PIP—own definition	33%	They detected 29 (0.9%) A, 380 (11.8%) B, 2494 (77.7%) C, 289 (9%) D, and 18 (0.6%) X risk rating category PIPs
Guthrie⁴¹ (2011)	UK PC	139,404 patients	“Particularly vulnerable” defined by age, pre-existing disease, or pre-existing coprescription.	PIP—STOPPPPO—START	13.9%
Jayaweera⁴² (2020)	US PC	111,461 PCPs who specialized in family medicine, internal medicine, general practice, and geriatric medicine	Medicare Part D patients	PIP—Beers	4.9%	PIP varied widely across PCPs with the bottom quartile at 1.2% and the top quartile at 10.1%
Kheir⁴³ (2014)	Qatar PC	52 patients, 175 DRPs were identified with an average of 3.4 DRPs per patient	No	DRP—own definition	3.4 DRPs per patient	The most commonly reported DRPs were nonadherence to drug therapy (31%), need for education and counseling (23%),and ADRs (21%)
Khoja⁴⁴ (2011)	Saudi Arabia PC	463 prescriptions from public clinics and 2836 from private clinics	No	“Prescription errors”—own definition	18.7%	Type B errors were detected in 8.0% versus 6.0% of drugs prescribed by public and private clinics, respectively, and type C errors were found in 2.2% versus 1.1% drugs prescribed by public and private clinics, respectively
Komagamine⁴⁵ (2018)	Japan hospital PC	671 patients	65+	PIP—Beers	54.8% in patients exempt from payment, 36.0% for others
Kovacevic⁴⁶ (2017)	Serbian PC	388 prescriptions	“Elderly” with polypharmacy	DRP—own definition	98.2% with at least one DRP
Kunac⁴⁷ (2014)	New Zealand PC	376 voluntary reports	No	Medication errors—own definition	14.7% of reports listed a patient harm
Miller⁴⁹ (2006)	Australian PC	8215 patients Each GP was asked to record whether or not each of 30 patients had experienced an ADE in the preceding 6 months	No	ADE—own definition; frequency of hospitalization	852 patients (10.4%) had experienced ADE	A GP severity rating for the most recent ADE was provided for 551 patients. Over half (53.9%) were rated as having a “mild” event(s), with a third rated as “moderate.” A “severe” rating was given for 55 patients (10.0% of those with an ADE or 6.7 per 1000 patients sampled). Responses to the question on hospitalization were received for 223 patients in survey 2. Of these, 7.6% (95% CI, 3.6 to 11.6) had been hospitalized as a result of the most recent ADE (9.7 per 1000 patients in the total sample). Preventability was judged for 327 patients in survey 3. GPs classified the ADE as preventable for 23.2% (95% CI, 17.4 to 29.1), made up of 19.9% of “mild” events, 25% of “moderate” and 32% of “severe” events
Oliveira⁵⁰ (2015)	Brazilian family health units	142 patients	Ages 60+	PIP—Beers, STOPP	33.8%-51.8%
Perez⁵¹ (2018)	Ireland PC	38,229 patients	Ages 65+	PIP—STOPP	45.3%-51.0%
Ryan⁵² (2009)	Ireland PC	500 patients	Ages 65+ and at least 1 medication	PIP—Beers and IPET	13%
Ryan⁵³ (2009)	Ireland PC	1329 patients	Ages 65+ and at least 1 medication	PIP—Beers, STOPP PPO—START	18.3%-21.4% 22.7%	177 (61.8%) of the potential PIPs identified were of “high severity”
Stocks⁵⁴ (2015)	UK PC	949,552 patients	No	PIP—own definition	5.26%
Trinkley⁵⁵ (2017)	Ohio University PC	1160 patients A pharmacist performed a comprehensive EHR review and conducted a telephone interview with each of the respective participants at 7-21 days (first screen) and 30- 60 days (second screen) following a medication change	No	ADE—own definition	Of the 701 participants and 1368 unique medication changes, 226 (32%) suspected ADEs were identified; 30% of the suspected ADEs were deemed to be “definite” or “probable” following causality assessment, 21% of the 68 ADEs were preventable, and 40% were ameliorable	All ADEs were considered significant; however, only 2 were serious or life-threatening
Wallace⁵⁶ (2017)	Ireland PC	605 patients for ADE interview; 662 patients for EQ-5 Days-3L questionnaire; 806 patients for chart review	Ages 70+	PIP—Beers, STOPP ADE—own definition HRQoL—Euro Quol-5 Dimensions (EQ-5 Days)-3L	40% STOPP 26% Beers 74% ≥ 1 ADE	In multivariable analysis ≥2 Beers 2012 PIP was not associated with ADEs (adjusted incidence rate ratio 1.00 [95% CI 0.78, 1.29]), poorer HRQoL (adjusted coefficient −0.05 [95% CI −0.11, 0.003]), A&E visits (adjusted OR 1.54 [95% CI 0.88, 2.71]), or emergency admission (adjusted OR 0.72 [95% CI 0.41, 1.28]). At baseline, the prevalence of ≥ 1 PIP was 40% (n = 243), with 362 (60%) participants prescribed no PIP, 142 (24%) 1 PIP, and 101 (16%) ≥ 2 PIPs
Wauters⁵⁷ (2016)	Belgium PC	503 patients in the Belfrail-Med cohort	Ages 80+	PIP—STOPP PPO—START	PIP 56% PPO 67%	Increase risk of hospitalization (HR 1.26) and mortality (HR 1.39) for underuse but not overuse
Wucherer⁵⁸ (2017)	Germany PC	446 patients	Ages 70+ with positive screening for dementia	DRP—PIE-Doc®-System	92.8%	Problems related to administration and compliance were the most common group of DRPs (59.9% of registered DRPs; n = 645), followed by problems with drug interactions (16.7%; n = 180), problems with inappropriate drug choice (14.7%; n = 158), problems with the dosage (6.2%; n = 67), and problems with ADEs (2.5%; n = 27)

Abbreviations: A&E, accident & emergency; ADE, adverse drug event; ADR, adverse drug reaction; Beers, Beer's criteria; DRP, drug-related problem; EHR, electronic health record; FORTA, fit for the aged; GP, general practitioner; HRQoL, health-related quality of life; IOM, Institute of Medicine; MAI, medication appropriateness index; PC, primary care; PCP, primary care physician; PIP, potentially inappropriate prescribing; PPO, potential prescribing omission; START, screening tool to alert to right treatment; STOPP, screening tool of old people's prescriptions.

View popup

Table 2.

Interventional Studies

Lead Author (Year)	Setting	Number of Patients or Prescriptions	High-Risk Subpopulation	Definition of Medical Error	Intervention	Error Rate	Other Outcomes
Benson⁵⁹ (2018)	Australian GP patients	493 patients	Polypharmacy (5+ medications), diabetes, adherence concerns, asthma/chronic obstructive pulmonary disease, inadequate response to therapy, suspected adverse reaction, patient request, pain management, recent hospital discharge, and medication with a narrow therapeutic index	DRP—own definition	Feedback by pharmacist to GP	1124 DRPs in 493 consultations, 685/984 (70%) recs accepted. 94% of patients had at least 1 DRP	Pharmacists made a total of 984 recommendations in relation to the 1140 DRPs identified, of which 685 (70%) were recorded as actioned by the GP Harms not measured
Clyne⁶⁰ (2015)	Ireland PC	196 patients	Ages 70+	PIP—own definition	Intervention GP participants received a complex, multifaceted intervention Control practices received simple, patient-level PIP feedback	Baseline PIP: 1.31 drugs/patient intervention group, 1.39 in control group Completion PIP: 100% to 52% in the intervention group,100% to 77% in the control group (P = .02) 0.7 PIP per patient intervention, 1.18 control (P = .02)	Harms not measured
Clyne⁶¹ (2016)	Ireland PC	196 patients—follow-up of primary study	Ages 70+	PIP—own definition	Pharmacist feedback as above.	51% patients with PIP in the intervention group, 76% in the control group (P = .01). The mean number of PIP drugs in the intervention group was 0.61, 1.03 in the control group (P = .01)	Harms not measured
Gibert⁶² (2018)	France PC	172 patients	Ages 75+ who were taking at least 5 drugs	PIP—STOPP	GPs taught to use STOPP criteria on their own patients	GP's intervention decreased the number of PIMs according to STOPP criteria to 106 and was beneficial for 44.9% of the patients (n = 44). The mean MAI score of all medications and PIMs decreased by 14.3% (P < .001) and 39.1% (P < .001) respectively	Harms not measured
Howard⁶³ (2014)	UK PC	72 general practices 2038 patient records reviewed	Taking one of 8 classes of potentially hazardous medications	Potentially hazardous prescribing—own definition	Intervention practices received simple feedback plus a pharmacist-led information technology complex intervention (PINCER) lasting 12 weeks	Pharmacists recommended 2105 interventions in 74% (95% CI 73, 76; 1516/2038) of cases and 1685 actions were taken in 61% (95% CI 59, 63; 1246/2038) of cases;control group not reported	Harms not measured
Leendertse⁶⁴ (2013)	Netherlands PC	364 intervention and 310 control patients	Patients with a high risk on medication-related hospitalizations based on old age, use of 5 or more medicines, nonadherence and type of medication used	Medication-related hospital admissions, ADE, survival, quality of life (EQ5D/Visual Analog scale).	The intervention consisted of a patient interview and evaluation of a pharmaceutical care plan. The patient's own pharmacist and GP carried out the intervention. The control group received usual care and was cared for by a GP other than the intervention GP	6 (1.6%) admissions in intervention group, 10 in control group (3.2%), p = NS	The secondary outcomes were not statistically significantly different either
Lenander⁶⁵ (2014)	Sweden PC	209 patients	Ages 65+ and 5+ medications	DRP—own definition	The pharmacist reviewed all medications (prescription, nonprescription, and herbal) regarding recommendations and renal impairment, giving advice to patients and GPs. Each patient met the pharmacist before seeing their GP.Control patients received their usual care	No significant difference was seen when comparing change in DRPs between the groups	Groups not balanced at beginning of trial. Harms not measured
Lopez-Picazo⁶⁶ (2011)	Spain PC	81,805 patients of 265 family physicians	No	Potentially serious drug interactions—own definition	Specially designed software analyzed EHR data and generated reports. Physicians and their patients randomized into 4 groups: control, report, sessions, and face-to-face personal interviews	Overall, a baseline mean of 6.7 interactions per 100 patients, which was reduced to 5.3 interactions after follow-up No difference between the control and report groups	Harms not measured
Peek⁶⁷ (2020)	UK PC	47,413 patients in 43 general practices	Have 1 or more risk factors for any of the 12 medication safety indicators at the start of the intervention	12 medication safety indicators (10 relating to potentially hazardous prescribing and 2 to inadequate blood-test monitoring) developed for PINCER	SMASH comprised (1) training of clinical pharmacists to deliver the intervention; (2) a web-based dashboard providing actionable, patient-level feedb ack; and (3) pharmacists reviewing individual at-risk patients and initiating remedial actions or advising general practitionerson doing so	At baseline, 95% of practices had rates of potentially hazardousprescribing (composite of 10 indicators) between 0.88% and 6.19%. The prevalence of potentially hazardous prescribing reduced by 27.9% (95% CI 20.3% to 36.8%, P < .001) at 24 weeks and by 40.7% (95% CI 29.1% to 54.2%, P < .001) at 12 months	Harms not measured
Singh⁶⁸ (2012)	New York PC	1125 patients preintervention; 1050 patients postintervention	Ages 65+	ADE—own definition	This was a cluster randomized trial in which 12 practices were each randomized to one of 3 states (4 practices each): (1) team resource management intervention; (2) team resource management intervention with PEA; (3) no intervention (comparison group).	In the “Intervention with PEA” group there was a statistically significant decrease in the overall rate of preventable ADEs after the intervention compared to before (7.4 per 100 patient-years vs 12.6, P = .018) and in the rate of moderate or severe (combined) preventable ADEs (1.6 vs 6.4, P = .035).	Examples of preventable errors include missed allergy, wrong dosage, errors of dispensing, administration errors, and failure to order or complete laboratory monitoring.Harms not measured.Groups were not balanced at baseline
Vanderman⁶⁹ (2017)	Veterans Affairs PC in North Carolina	1539 patients preinterv ention; 1490 patients postintervention	Ages 65+	PIP—Beers	Computerized physician order entry in Epic EHR	PIP rate 12.6% preintervention, 12.0% post (p = NS)	Top 10 PIPs 9.0% to 8.3%, (P = .016) Harms not measured
Wessell⁷⁰ (2008)	South Carolina PC	124,802 patients	Ages 65+	PIP—Beers	Quarterly performance reports, on-site visits, and annual meetings for 4 years	Always inappropriate 0.41% to 0.33%, rarely appropriate medication decreased from 1.48% to 1.30%	Harms not measured
Wessell⁷¹ (2013)	20 PC sites in 14 US states	49,047 patients	High-risk medication use based on 44 indicators	PIP—own definition	Local performance review, quarterly reports, and academic detailing	Improved 3/5 measures by 2.9% to 4.0%; 2/5 measures unchanged over 2 years	Harms not measured

Abbreviations: ADE, adverse drug event; Beers, Beer's criteria; DRP, drug-related problem; EHR, electronic health record; GP, general practitioner; MAI, medication appropriateness index; PC, primary care; PEA, practice enhancement associate; PIM, potentially inappropriate medication; PIP, potentially inappropriate prescribing; STOPP, screening tool of old people's prescriptions.