Table 2.

Study design, associations of investigated factors with of potentially inappropriate medication (PIM) and risk of bias^a

Author, year Study design	Criteria used to define PIM	Patient factors	System/Environment factors	Clinician factors	Risk of bias
Administrative data
Zhang (2010)[27] Cross-sectional	HEDIS medications considered to be high risk and potential drug–disease interactions	None	Adjusted annual gross drug spending per beneficiary and adjusted annual gross non-drug medical spending [higher non-drug spending]	None	Low
Woelfel (2011)[20] Cross-sectional	Beers Criteria 1997	Age, sex, self-reported health status, number of medications per patient [higher]	None	None	Low
Blackwell (2012)[29] Cross-sectional	Beers Criteria 2003 excluding those with dose requirements or disease requirements	Age [65–74, ref: 75+], race/ethnicity [white, ref: black/other] sex [female, ref: male], disease burden [low, ref: medium-low], number of medications [higher]	Geographic region [midwest, south, west, other, ref: northeast], dual enrollee status [ref: non-dual enrollee]	None	Low
Holmes (2013)[31] Cross-sectional	Beers Criteria 2003 – excluding drug-disease combinations	Age, sex [female, ref: male], race/ethnicity [black, ref: white], hospitalization in the year prior to PIM use (2007) [not hospitalized at least once, ref: hospitalized at least once] nursing home stay in 2008, comorbidity score (Elixhauser), total number of medications in 2008 [six or more medications, ref: <5 medications], number of different prescribers [two or more prescribers, ref: 1 prescriber]	Eligibility for low-income subsidy [eligible, ref: not eligible]	None	Low
Lund (2013)[32] Cross-sectional	Four methods: Zhan Criteria, modified Fick Criteria, therapeutic duplication, drug–drug interactions	None	Zhan criteria: rural [ref: urban], midwest, west, south [ref: northeast], Rural northeast [ref: urban northeast], urban midwest [ref: rural midwest], urban west [ref: rural west], rural south [ref: urban south] Fick criteria: rural [ref: urban], midwest, west, south [ref: northeast], Rural northeast [ref: urban northeast], rural midwest, urban west [ref: rural west], rural south [ref: urban south]	None	Low
Jiron (2016)[35] Retrospective cohort	Beers Criteria 2012 – all medications inappropriate and all medications to be used with caution	Age [66–69 years, ref: 70+], sex [female, ref: male], race [white, ref: Asian, Hispanic], myocardial infarction [absence, ref: presence], CHF [presence, ref: absence], peripheral vascular disease, cerebrovascular disease [presence, ref: absence] dementia [presence, ref: absence], chronic obstructive pulmonary disease, rheumatic disease, peptic ulcer disease [presence, ref: absence] mild liver disease, diabetes without complications [presence, ref: absence], paraplegia and haemiplegia [presence, ref: absence] renal disease [absence, ref: presence], diabetes with chronic complications, cancer [absence, ref: presence], moderate or severe liver disease [presence, ref: absence], metastatic cancer, AIDS/HIV, polypharmacy, number of prescription medications filled per month [3 or more, ref: less than 3], number of outpatient visits [13+, ref: >13], number of ED visits [1 or more, ref: none], number of hospital visits, any hospital admission, any outpatient visits, number of prescribers per month [2 or more, ref: less than 2], number of prescriber specialties per month	Geographic region [south or west, ref: northeast]	Prescriber is a geriatrician [is a geriatrician, ref: provider is not a geriatrician], general practitioner/family practice/internist, other specialty	Low
Kester (2016)[36] Prospective cohort	Antipsychotic medications (1st and 2nd generation)	Age [higher], sex [female, ref: male], hierarchical condition category, diagnosis of depressive disorder [presence, ref: absence], diagnosis of substance use disorder [presence, ref: absence]	Geographic region [south, ref: midwest, west], dual eligible status [ref: non-dual eligible]	None	Low
Chart review
Buck (2008)[25] Cross-sectional	Beers Criteria 2002 and Zhan Criteria independent of diagnoses	Age [older], sex [female, ref: male], polypharmacy [>6 medications, ref: <6], race, number of primary care clinic visits [more visits]	None	None	Low
Hu (2012)[28] Cross-sectional	Beers Criteria 2002 excluding disease dependent	Age [81+, ref: <81], sex, education, marital status, post-hospital residence, primary language, English proficiency, Chinese proficiency, number of medications at discharge [≥ 8 medications, ref: <8], number of medications at home care admission, length of hospital stay [≥6 days, <6 days]	Hospitalized on medical unit	None	Low
Prithviraj (2012)[30] Cross-sectional	Beers Criteria 2003 excluding drug–disease interactions	Age, sex, race, marital status, education, living situation, body mass index [≥19, ref: body mass index <19], cancer type, cancer stage, receipt of surgery, comorbidity count, Charlson comorbidity index, Eastern Cooperative Oncology Group (ECOG) score, hearing and vision impairment on 5-point scale, patient self-reported falls in the last 6 months, MMSE, number of medications [≥5 medications, ref: <5 medications], Geriatric depression scale, medical outcomes study social support survey, composite variable ‘geriatric deficits’ (≥1 deficit in MMSE, geriatric depression scale, hearing and vision questionnaire, social support survey)	None	None	Low
Nightingale (2015)[39] Cross-sectional	Beers 2012, STOPP 2008 and HEDIS 2011	Age, sex, race, cancer type and stage, number of comorbidities [higher], Eastern Cooperative Oncology Group (ECOG) performance status, functional status (fit, vulnerable, frail), moderate polypharmacy [5–9 medications, ref: <5 medications], excessive polypharmacy [10+ medications, ref: <5 medications], presence of comorbidities [cardiovascular, neurologic, psychiatric, gastrointestinal]	None	None	Moderate
DiNapoli (2016)[34] Prospective cohort	Online drug database (clinicalpharmacology.com Elsevier Gold Standard) and VA provider input	Age, race, marital status, two or more mental health diagnoses [ref: 1], number of chronic organ system diseases	VA service connection status	None	Low
Ie (2017)[40] Cross-sectional	Beers Criteria, 2015	None	None	Lack of benefit/risk information about deprescribing is a barrier to deprescribing, number of medications, proportion of minority patients [low, ref: high], proportion of patients ≥75 [low, ref: high], use of the beers list	Moderate
Nationally representative survey
Zhang (2011)[21] Cross-sectional	Zhan criteria	Age, sex [female, ref: male], race/ethnicity, family income [middle, ref: high], education level, self-rated health [fair, poor, ref: excellent], number of prescriptions [higher]	Medicare status, Medicare part D coverage, metropolitan statistical area, geographic region [south, ref: northeast]	None	Low
Kachru (2015)[22] Cross-sectional	Beers Criteria 2012, anticholinergics only	Age [<74, ref: age>75], sex [female], race, marital status, education [<12 years of education, ref: >15 years], family income, usual source of care, needs help with ADLs, needs help with iADLs, self-reported health, mental health status, comorbidities: epilepsy, dementia, fractures, Parkinson’s, benign prostatic hyperplasia, CHF, arrhythmia, mood disorder, anxiety [presence, ref: absence], urinary incontinence	Metropolitan statistical area, geographic region, [south, ref: northeast]	None	Low
Extavour (2016)[24] Cross-sectional	Beers Criteria 2012/2015 Sedatives or Antidepressants	Sedative hypnotics: sex [female, ref: male],race [white, ref: other], ethnicity, chronic renal failure [absence, ref: presence], depression [presence, ref: absence], diabetes [absence, ref: presence], obesity [absence, ref: presence], chronic obstructive pulmonary disease, number of medications [higher],household income [40,627–52,387, ref: highest income] Antidepressants: race [other, ref: white], depression [absence, ref: presence], asthma [absence, ref: presence], osteoporosis [absence, ref: presence], annual household income	Sedative hypnotics: practice ownership, use of electronic health record Antidepressants: metropolitan statistical area, computer system features prescribing [no, ref: yes] payment type [private self-pay, ref: other], payment type (Medicare Medicaid)	Sedative hypnotics: specialty [neurology, ref: other], [psychiatry, ref: other], physician assistant involvement Antidepressants: time spent with patient [less time], physician specialty	Low
Miller (2016)[23] Cross-sectional	Beers Criteria 2012	Age [65–74 ref: 75–84, 85+], sex, race, marital status, education [less than high school, ref: high school graduate or post-graduate education], income, risk taking, usual source of care, self-rated health status, self-rated mental health status, ADL limitations, iADL limitations, cardiovascular condition [absence, ref: presence], central nervous system condition, mental health disorder, arthritis [presence, ref: absence], diabetes; number of medications [higher]	geographic region, metropolitan statistical area, health insurance status	None	Low
Swanoski (2017)[37] Survey	Beers 2012 criteria, drugs inappropriate in diabetes	Age [75+, ref: 65–74], sex [female, ref: male], race/ethnicity [all other races/ethnicities, ref: non-Hispanic Caucasian], visit reason [other, ref: new problem], visit reason [chronic problem, routine, ref: other], visit reason [chronic problem, flare-up, ref: other], visit reason [preventive care, ref: other], two or more visits in year [ref: one or fewer]	Geographic region of physician [rural, ref: urban]	None	Low
Other
Weston (2010)[26] Cross-sectional	Beers Criteria 2003 inappropriate in cognitive impairment, additional medications per authors’ discretion	Age, race/ethnicity, sex [female, ref: male], education, living situation, number of medications [higher], functional status, MMSE score, history of hypertension, urinary incontinence, history of diabetes, anti-dementia drug use, history of stroke, history of myocardial infarction, history of depression [presence, ref: absence]	Insurance status	None	Low
Koyama (2013)[33] Prospective cohort	Beers Criteria 2003 inappropriate in cognitive impairment, additional medications per authors’ discretion	Cognitive status (dementia versus mild cognitive impairment versus normal) [at 10-year follow-up, dementia>mild cognitive impairment> normal cognition]	None	None	Low
Mattos (2016)[38] Cross-sectional	Benzodiazepine receptor agonists and non-benzodiazepine sleep aids	Age, sex, race, marital status, depression or anxiety diagnosis [presence, ref: absence], total number of medications [higher], level of education	Rural [ref: urban]	None	Moderate
Shade (2017)[41] Cross-sectional	Beers 2012	Age, comorbidity score, mental component score, total sleep time, wake after sleep onset, wake percentage, PROMIS Number of medications [higher], number of prescribers, physical component score, Pittsburgh sleep quality index	None	None	Low

ADL, activities of daily living; CHF, congestive heart failure; ED, emergency department; HEDIS, Healthcare Effectiveness Data and Information Set; iADL, independent activity of daily living; MCO, managed care organization; MDS, minimum data set; MEPS, Medical Expenditure Panel Survey; MMSE, Mini-Mental State Exam; NAMCS, National Ambulatory Medical Care Survey; PIM, potentially inappropriate medications; Ref, reference group; VA, veterans affairs.

^aBold – significant factors [positive association with PIM use].