Review ArticleSystematic Reviews

Potentially Inappropriate Prescribing Among Older Persons: A Meta-Analysis of Observational Studies

Tau Ming Liew, Cia Sin Lee, Kuan Liang Goh Shawn and Zi Ying Chang
The Annals of Family Medicine May 2019, 17 (3) 257-266; DOI: https://doi.org/10.1370/afm.2373

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  • Table 1.

    Key Characteristics of the Studies Included in the Systematic Review

    Risk of Bias (Newcastle-Ottawa Scale)a
    Author (Year)Sampling MethodSample SizeAge, Years% FemaleFollow-Up Duration in YearsData Source of PIPCriteria of PIPData Source of OutcomesSelection (Max 4*)Comparability (Max 2*)Outcome (Max 3*)
    Barnett et al,27 2011Whole population registry70,299Mean 75.2
    SD 6.8    		57.02.0Dispensed prescribing databaseBeers Criteria 2003Mortality: Death certification database* * * ** ** * *
    Cahir et al,25 2014
    Cahir et al,24 2014    		Stratified random sampling931Mean 78.0
    SD 5.4    		54.00.5Pharmacy claim databaseBeers Criteria 2012
    STOPP    		ADEs, hospitalizations, and A&E visits: Structured interview and medical records
    Functional decline: VES scale HRQoL: EQ-5D scale    		* * * ** ** * *
    Hanlon et al,25 2002
    Fillenbaum et al,26 2004    		Stratified probability sampling3,23465-74 years: 49.1%
    75-84 years: 41.1%
    ≥85 years: 9.8%    		64.83.0Structured interviewBeers Criteria 1997
    DUR    		Mortality: National Death Index
    Functional decline: Combination of Katz ADL, OARS Instrumental ADLs, and abbreviated Rosow-Breslau scale
    Hospitalizations: Medicare and Medicaid database
    Outpatient visits and nursing home entry: self-or proxy report    		* * * ** ** * *
    Moriarty et al,28 2016Stratified random sampling1,753Mean 76.5
    SD 6.0    		54.41.0Pharmacy claim databaseSTOPP
    START    		A&E visits, GP visits: Structured interview
    Functional decline: Difficulty in doing 6 named ADLs HRQoL: CASP-R12 scale    		* * * ** ** * *
    Wallace et al,29 2017Stratified random sampling904Median 77
    IQR 74-81    		54.02.0Pharmacy claim databasesBeers Criteria 2012
    STOPP    		ADEs: Patient interview and medical records
    A&E visits and hospitalizations: Medical records HRQoL: EQ-5D scale    		* * * ** ** * *
    Wauters et al,30 2016Whole GP registry and consecutive sampling503Mean 84.461.21.5Secured recordSTOPP
    START    		Mortality: Secured record
    Hospitalizations: Secured record    		* * * *** * *

    • A&E = accident and emergency department; ADE = adverse drug event; ADL = activity of daily living; CASP-R12 = control, autonomy, self-realization, and pleasure revised 12-item quality of life scale; DUR = drug utilization review; EQ-5D = health-related quality of life states consisting of 5 dimensions; GP = general practitioner; HRQoL = health-related quality of life; IQR = interquartile range; OARS = Older American Resources and Service; PIP = potentially inappropriate prescribing; START = Screening Tool to Alert Right Treatment; STOPP = Screening Tool of Older Persons’ Potentially Inappropriate Prescriptions; VES = Vulnerable Elders Survey.

    • ↵a A star (*) is awarded if a specific criterion in the Newcastle-Ottawa Scale was met, indicating low risk of bias in that criterion. Further details on the Newcastle-Ottawa Scale are available in the supplemental appendix, available at http://www.AnnFamMed.org/content/17/3/257/suppl/DC1/.

  • Table 2

    Covariates That Were Adjusted for in the Statistical Models of the Included Studies

    Adjusted Covariate Adjusted Covariate
    Author (Year)AgeSexSocioeconomic statusComorbiditiesNumber of MedicationsMedication AdherenceEducationRaceFunctional StatusCognitive ImpairmentSocial SupportPrior Healthcare UtilizationMental Health ConditionOther
    Barnett et al,27 2011✓✓✓–✓–––––––––
    Cahir et al,23 2014✓✓✓✓✓✓––––✓––Sex of the general practitioner
    Cahir et al,24 2014✓✓✓✓✓✓––––✓––Sex of the general practitioner
    Hanlon et al,25 2002✓✓✓✓✓–✓✓✓✓–––Body mass index
    Fillenbaum et al,26 2004✓✓✓✓––✓✓✓✓–✓–Marital status, insurance coverage
    Moriarty et al,28 2016✓✓–✓✓–✓–––✓✓✓Insurance coverage
    Wallace et al,29 2017✓✓✓✓✓✓✓––––✓✓–
    Wauters et al,30 2016––––✓–––––––––
  • Table 3

    Summary of Key Findings and GRADE Assessment

    GRADE Assessment
    OutcomesLarge Effectf/Dose ResponsegPooled Effect Size(95% CI)Certainty of Evidence GRADERisk of BiasaInconsistencybImprecisionc/Publication Biasd/IndirectnesseLarge Effectf/Dose Responseg
    PIP based on the Beers Criteria
    Functional decline4,165RR 1.38
    (1.06-1.80)    		●●○○○
    Low    		No downgrade
    (NOS = 9)    		No downgrade
    (I2 = 29.5%, P= .234)    		No downgradeNo upgrade
    Hospitalizations5,069RR 1.14
    (1.01-1.29)    		●●○○○
    Low    		No downgrade
    (NOS = 9)    		No downgrade
    (I2 = 37.0%,P = .204)    		No downgradeNo upgrade
    Mortality73,533RR 0.98
    (0.93-1.05)    		●●○○○
    Low    		No downgrade
    (NOS = 9)    		No downgrade
    (I2 = 0.0%, P = .689)    		No downgradeNo upgrade
    PIP based on the STOPP criteria
    A&E visits3,588RR 1.63
    (1.32-2.00)    		●●○○○
    Low    		No downgrade
    (NOS = 9)    		No downgrade
    (I2 = 0.0%, P = .452)    		No downgradeNo upgrade
    ADEs1,835RR 1.34
    (1.09-1.66)    		●●○○○
    Low    		No downgrade
    (NOS = 9)    		No downgrade
    (I2 = 41.3%, P = .192)    		No downgradeNo upgrade
    Functional decline2,684RR 1.53
    (1.08-2.18)    		●●○○○
    Low    		No downgrade
    (NOS = 9)    		No downgrade
    (I2 = 17.6%, P= .271)    		No downgradeNo upgrade
    HRQoL3,588SMD -0.26
    (−0.36 to −0.16)    		●○○○○
    Very low    		No downgrade
    (NOS = 9)    		Downgrade
    (I2 = 82.3%, P = .003)    		No downgradeNo upgrade
    Hospitalizations2,338RR 1.25
    (1.09-1.44)    		●●○○○
    Low    		No downgrade
    (NOS = 8)    		No downgrade
    (I2 = 53.6%, P =.116)    		No downgradeNo upgrade

    • A&E = accident and emergency department; ADE = adverse drug event; GRADE = Grading of Recommendations, Assessment, Development and Evaluations; HRQoL = health-related quality of life; NOS = Newcastle-Ottawa Scale; PIP = potentially inappropriate prescribing; RR = relative risk; SMD = standardized mean difference; STOPP = Screening Tool of Older Persons’ Potentially Inappropriate Prescriptions.

    • ↵a We downgraded the GRADE assessment if the risk of bias assessment based on the NOS is <8 in at least one of the studies, suggesting the presence of risk of bias.

    • ↵b We downgraded the GRADE assessment if the Q test P < 0.10 or the I2 > 75%, indicating significantly high levels of heterogeneity in the results.

    • ↵c For RR, we considered a clinically meaningful threshold to be 0.90 or 1.10 and downgraded the GRADE assessment if the RR point estimate is ≥1 and the lower limit of its CI is <0.90, or if the RR point estimate is <1 and the upper limit of its CI is >1.10. For SMD, we considered a clinically meaningful threshold to be ±0.20 and downgraded the GRADE assessment if the point estimate is ≥0 and the lower limit of its CI is <–0.20, or if the point estimate is <0 and the upper limit of its CI is >0.20.

    • ↵d We could not assess for publication bias because there were <10 studies for each of the outcomes. Therefore, we did not downgrade any of the GRADE assessments due to publication bias.

    • ↵e We downgraded the GRADE assessment if the recruited participants were not representative of older persons in the primary care settings.

    • ↵f We upgraded the GRADE assessment if the RR is >2 or <0.5.

    • ↵g We upgraded the GRADE assessment in the presence of dose-response gradient, which provides stronger evidence of the cause-effect relationship.

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  • The Article in Brief

    Potentially Inappropriate Prescribing Among Older Persons: A Meta-Analysis of Observational Studies

    Tau Ming Liew , and colleagues

    Background Potentially inappropriate prescribing (the prescribing or under-prescribing of medications) is a common yet preventable medical error. This study examines whether such prescribing produces adverse outcomes in older primary care patients.

    What This Study Found In older adults, inappropriate prescribing in primary care is associated with a wide range of adverse outcomes, but not mortality. An analysis of existing studies looked at potentially inappropriate prescribing in older persons that could cause significant harm. The analysis found that, although potentially inappropriate prescribing did not affect mortality, it was significantly associated with emergency room visits, adverse drug events, functional decline, health-related quality of life, and hospitalizations.

    Implications

    • According to the authors, the findings highlight the need to address potentially inappropriate prescribing in primary care. They call for further research into effective interventions, and they call on researchers to consider the potential implications of how potentially inappropriate prescribing is operationalized in their work.
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