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Potentially inappropriate medications (PIMs) continue to be prescribed and used as first-line treatment for the most vulnerable of older adults, despite evidence of poor outcomes from the use of PIMs in older adults. PIMs now form an integral part of policy and practice and are incorporated into several quality measures. The specific aim of this project was to update the previous Beers Criteria using a comprehensive, systematic review and grading of the evidence on drug-related problems and adverse drug events (ADEs) in older adults. This was accomplished through the support of The American Geriatrics Society (AGS) and the work of an interdisciplinary panel of 11 experts in geriatric care and pharmacotherapy who applied a modified Delphi method to the systematic review and grading to reach consensus on the updated 2012 AGS Beers Criteria. Fifty-three medications or medication classes encompass the final updated Criteria, which are divided into three categories: potentially inappropriate medications and classes to avoid in older adults, potentially inappropriate medications and classes to avoid in older adults with certain diseases and syndromes that the drugs listed can exacerbate, and finally medications to be used with caution in older adults. This update has much strength, including the use of an evidence-based approach using the Institute of Medicine standards and the development of a partnership to regularly update the Criteria. Thoughtful application of the Criteria will allow for (a) closer monitoring of drug use, (b) application of real-time e-prescribing and interventions to decrease ADEs in older adults, and (c) better patient outcomes.
Medication-related problems are common, costly, and often preventable in older adults and lead to poor outcomes. Estimates from past studies in ambulatory and long-term care settings found that 27% of adverse drug events (ADEs) in primary care and 42% of ADEs in long-term care were preventable, with most problems occurring at the ordering and monitoring stages of care.1,2 In a study of the 2000/2001 Medical Expenditure Panel Survey, the total estimated healthcare expenditures related to the use of potentially inappropriate medications (PIMs) was $7.2 billion.3
Avoiding the use of inappropriate and high-risk drugs is an important, simple, and effective strategy in reducing medication-related problems and ADEs in older adults. Methods to address medication-related problems include implicit and explicit criteria. Explicit criteria can identify high-risk drugs using a list of PIMs that have been identified through expert panel review as having an unfavorable balance of risks and benefits by themselves and considering alternative treatments available. A list of PIMs was developed and published by Beers and colleagues for nursing home residents in 1991 and subsequently expanded and revised in 1997 and 2003 to include all settings of geriatric care.4–6 Implicit criteria may include factors such as therapeutic duplication and drug–drug interactions. PIMs determined by explicit criteria (Beers Criteria) have also recently been found to identify other aspects of inappropriate medication use identified by implicit criteria.7
As summarized in two reviews, a number of investigators in rigorously designed observational studies have shown a strong link between the medications listed in the Beers Criteria and poor patient outcomes (e.g., ADEs, hospitalization, mortality).7–14 Moreover, research has shown that a number of PIMs have limited effectiveness in older adults and are associated with serious problems such as delirium, gastrointestinal bleeding, falls, and fracture.8,12 In addition to identifying drugs for which safer pharmacological alternatives are available, in many instances a safer nonpharmacological therapy could be substituted for the use of these medications, highlighting that a “less-is-more approach” is often the best way to improve health outcomes in older adults.15
Since the early 1990s, the prevalence of PIM usage has been examined in more than 500 studies, including a number of long-term care, outpatient, acute care, and community settings. Despite this preponderance of information, many PIMs continue to be prescribed and used as first-line treatment for the most vulnerable of older adults.16,17 These studies illustrate that more work is needed to address the use of PIMs in older adults, and there remains an important role in policy, research, and practice for an explicit list of medications to avoid in older adults. Because an increasing number of interventions have been successful in decreasing the use of these drugs and improving clinical outcomes,18,19 PIMs now form an integral part of policy and practice in the Centers for Medicare and Medicaid Services (CMS) regulations and are used in Medicare Part D. They are also used as a quality measure in the National Committee for Quality Assurance (NCQA) Healthcare Effectiveness Data and Information Set (HEDIS). Several stakeholders, including CMS, NCQA, and the Pharmacy Quality Alliance (PQA) have identified the Beers Criteria as an important quality measure. In addition, a few studies have begun to identify nonpharmacological alternatives to inappropriate medications20 and are incorporating Beers Criteria PIMs into electronic health records as an aid to real-time e-prescribing.19
An update of the Beers Criteria should include a clear approach to reviewing and grading the evidence for the drugs to avoid. In addition, the criteria need to be regularly updated as new drugs come to the market, as new evidence emerges related to the use of these medications, and as new methods to assess the evidence develop. Being able to update these criteria quickly and transparently is crucial to their continued use as decision-making tools, because regular updates will improve their relevancy, dissemination, and usefulness in clinical practice.
The 2012 update of the Beers Criteria heralds a new partnership with the American Geriatrics Society (AGS). This partnership allows for regular, transparent, systematic updates and support for the wider input and dissemination of the criteria by expert clinicians for their use in research, policy, and practice. To keep this tool relevant, the updated 2012 AGS Beers Criteria must be current with other methods for determining best-practice guidelines. A rigorous systematic review was performed to update and expand the criteria. As in the past, this update will categorize PIMs into two broad groups: medications to avoid in older adults regardless of diseases or conditions and medications considered potentially inappropriate when used in older adults with certain diseases or syndromes. A third group, medications that should be used with caution, has been added. Medications in this group were initially considered for inclusion as PIMs. In these cases, the consensus view of the panel (described below) was that there were a sufficient number of plausible reasons why use of the drug in certain individuals would be appropriate but that the potential for misuse or harm is substantial and thus merits an extra level of caution in prescribing. In some cases, these medications were new to the market, and evidence was still emerging.
The specific aim is to:
Update the previous Beers Criteria using a comprehensive, systematic review and grading of the evidence on drug-related problems and ADEs in older adults.
The strategies to achieve this aim are to:
The 2012 AGS Beers Criteria are intended for use in all ambulatory and institutional settings of care for populations aged 65 and older in the United States. The primary target audience is the practicing clinician. Researchers, pharmacy benefit managers, regulators, and policy-makers also use the criteria widely. The intentions of the criteria include improving the selection of prescription drugs by clinicians and patients, evaluating patterns of drug use within populations, educating clinicians and patients on proper drug usage, and evaluating health-outcome, quality of care, cost, and utilization data.
The goal of the 2012 AGS Beers Criteria is to improve care of older adults by reducing their exposure to PIMs. This is accomplished by their use as an educational tool and a quality measure—two uses that are not always in agreement. These criteria are not meant to be applied in a punitive manner. Prescribing decisions are not always clear cut, and clinicians must consider multiple factors. Quality measures must be clearly defined, easily applied, and measured with limited information. The panel considered both roles during deliberations. The panel's review of evidence at times identified subgroups of individuals who should be exempt from the criteria or for whom only a specific criterion applies. Such a criterion may not be easily applied as a quality measure. These applications were balanced with the needs and complexities of the individual. The panel felt that a criterion could not be expanded to include all adults aged 65 and older when only individuals with specific characteristics may benefit or be at greater risk of harm.
For this new update, the AGS employed a well-tested framework that has long been used for development of clinical practice guidelines.6,21–23 Specifically, the framework involved the appointment of an 11-member interdisciplinary expert panel with relevant clinical expertise and experience and an understanding of how the criteria have been previously used. To ensure that potential conflicts of interest are disclosed and addressed appropriately, panelists disclosed potential conflicts of interest with the panel at the beginning. Each panelist's potential conflict of interests are provided toward the end of this article. This framework also involved a development process that included a systematic literature review and evaluation of the evidence base by the expert panel. Finally, the Institute of Medicine's 2011 report on developing practice guidelines,23 which included a period for public comments, guided the framework. These three framework principles are described in greater detail below.
The literature from December 1, 2001 (the end of the previous panel's search) to March 30, 2011, was searched to identify published systematic reviews and meta-analyses that were relevant to the project. Search terms included adverse drug reactions, adverse drug events, medication problems, polypharmacy, inappropriate drug use, suboptimal drug therapy, drug monitoring, pharmacokinetics, drug interactions, and medication errors. Terms were searched alone and in combination. Search limits included human subjects, English language, and aged 65 and older. Data sources for the initial search included Medline, the Cochrane Library (Cochrane Database of Systematic Reviews), International Pharmaceutical abstracts, and references lists of selected articles that the panel co-chairs identified.
The initial search identified 25,549 citations, of which 6,505 were selected for preliminary review. The panel co-chairs reviewed 2,267 citations, of which 844 were excluded for not meeting the study purpose or not containing primary data. An additional search was conducted with the additional terms drug–drug and drug–disease interactions, pharmacoepidemiology, drug safety, geriatrics, and elderly prescribing. An additional search for randomized clinical trials and postmarketing and observational studies published between 2009 and 2011 was conducted using terms related to major drug classes and conditions, delimited by more-general topics (e.g., adverse drug reactions, Beers Criteria, suboptimal prescribing, and interventions). Previous searches were used to develop additional terms to be included in subsequent searches, such as a list of authors whose work was relevant to the goals of the project. When evidence was sparse on older medications, searches were conducted on drug class and individual medication names and included older search dates for these drugs. The co-chairs continually reviewed the updated search results for articles that might be relevant to the project. Panelists were also asked to forward pertinent citations that might be useful for revising the previous Beers Criteria or supporting additions to them.
At the time of the panel's face-to-face meeting, the co-chairs had selected 2,169 unduplicated citations for the full panel review. This total included 446 systematic reviews or meta-analyses, 629 randomized controlled trials, and 1,094 observational studies. Additional articles were found in a manual search of the reference lists of identified articles and the panelist's files, book chapter, and recent review articles, with 258 citations selected for the final evidence tables to support the list of drugs to avoid.
After consultation with the AGS, the co-chairs identified prospective panel members with recognized expertise in geriatric medicine, nursing, pharmacy practice, research, and quality measures. Other factors that influenced selection were the desire to have interdisciplinary representation, a range of medical specialties, and representation from different practice settings (e.g., long-term care, ambulatory care, geriatric mental health, palliative care and hospice). In addition to the 11-member panel, representatives from CMS, NCQA, and PQA were invited to serve as exofficio members.
Each expert panel member completed a disclosure form that was shared with the entire panel before the process began. Potential conflicts of interest were resolved by the panel co-chairs and were available during the open comment period. Panel members who disclosed affiliations or financial interests with commercial entities are listed under the disclosures section of this article.
The co-chairs and AGS staff edited the survey used in the previous Beers Criteria development process, excluding products no longer marketed. The resulting survey had three parts: medications currently listed as potentially inappropriate for older adults independent of diseases or conditions, medications currently listed as potentially inappropriate when used in older adults with certain diseases or conditions, and new submissions from the panel. Each panelist was asked to complete the survey using a 5-point Likert scale ranging from strongly agree to strongly disagree (or no opinion). Ratings were tallied and returned to the panel along with each panelist's original ratings. Two conference calls allowed for review of survey ratings, discussion, and consensus building.
The panel convened for a 2-day in-person meeting on August 2 and 3, 2011, to review the second draft of the survey and the results of the literature search. Panel discussions were used to define terms and to address questions of consistency, the inclusion of infrequently used drugs, the best strategies for evaluating the evidence, and the consolidation or expansion of individual criterion. The panel then split into four groups, with each assigned a specific set of criteria for evaluation. Groups were assigned as closely as possible according to specific area of clinical expertise (e.g., cardiovascular, central nervous system). Groups reviewed the literature search, selected citations relevant to their assigned criteria, and determined which citations should be included in an evidence table. During this process, panelists were provided copies of abstracts and full-text articles. The groups then presented their findings to the full panel for comment and consensus. After the meeting, each group met in a conference call to resolve any questions or to include additional supporting literature.
An independent researcher prepared evidence tables, which were distributed to the four criteria-specific groups. Each panelist independently rated the quality of evidence and strength of recommendation for each criterion using the American College of Physicians' Guideline Grading System24 (Table 1), which is based on the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) scheme developed previously.25 AGS staff compiled the panelist ratings for each group and returned them to that group, which then reached consensus in conference call. Additional literature was obtained and included as needed. When group consensus could not be reached, the full panel reviewed the ratings and worked through any differences until they reached consensus. For some criteria, the panel provided a “strong” recommendation even though the quality of evidence was low or moderate. In such cases, the strength of recommendation was based on potential severity of harm and the availability of treatment alternatives.
Fifty-three medications or medication classes encompass the final updated 2012 AGS Beers Criteria, which are divided into three categories (Tables 2–4). Tables were constructed and organized according to major therapeutic classes and organ systems.
Table 2 shows the 34 potentially inappropriate medications and classes to avoid in older adults. Notable new additions include megestrol, glyburide, and sliding-scale insulin.
Table 3 summarizes potentially inappropriate medications and classes to avoid in older adults with certain diseases and syndromes that the drugs listed can exacerbate. Notable new inclusions are thiazolidinediones or glitazones with heart failure, acetylcholinesterase inhibitors with history of syncope, and selective serotonin reuptake inhibitors with falls and fractures.
Table 4 lists medications to be used with caution in older adults. Fourteen medications and classes were categorized. Two of these involve recently marketed anti-thrombotics for which early evidence suggests caution for use in adults aged 75 and older.
Table 5 is a summary of medications that were moved to another category or modified since the last update, and Tables 6 and and77 summarize medications that were removed or added since the last update. Nineteen medications and medication classes were dropped from the 2003 to the 2012 update of the criteria based on consensus of the panel and evidence or a rationale to justify their exclusion from the list. In several cases, medications were removed because they had been taken off the U.S. market since the 2003 update (e.g., propoxyphene) or because of insufficient or new evidence that was evaluated by the panel (e.g., ethacrynic acid). Table 8 includes a list of the antipsychotics included in the statements. Table 9 is the list of anticholinergic medications to be avoided in older adults compiled from drugs rated as having strong anticholinergic properties in the Anticholinergic Risk Scale,26 Anticholinergic Drug Scale,27 and Anticholinergic Burden Scale.28
The 2012 AGS Beers Criteria is an important and improved update of previously established criteria widely used by healthcare providers, educators, and policy-makers and as a quality measure. Previously, as many as 40% of older adults received one or more medications on this list, depending on the care setting.29–31 The new criteria are based upon methods for determining best-practice guidelines that included a rigorous systematic literature review, the use of an expert consensus panel, and grading of the strength of evidence and recommendations.
The updated criteria should be viewed as a guideline for identifying medications for which the risks of their use in older adults outweigh the benefits. The medications that have a high risk of toxicity and adverse effects in older adults and limited effectiveness, and all medications in Table 2 (Independent of Diagnosis or Condition) should be avoided in favor of an alternative safer medication or a nondrug approach. The drug–disease or –syndrome interactions summarized in Table 3 are particularly important in the care of older adults because they often take multiple medications for multiple comorbidities. Their occurrence may have greater consequences in older adults because of age-related decline in physiological reserve. Recent studies in which drug–disease interactions have been shown to be important risk factors for ADEs highlight their importance.32
This list is not meant to supersede clinical judgment or an individual patient's values and needs. Prescribing and managing disease conditions should be individualized and involve shared decision-making. The historical lack of inclusion of many older adults in drug trials33–35 and the related lack of alternatives in some individual instances further complicate medication use in older adults. There may be cases in which the healthcare provider determines that a drug on the list is the only reasonable alternative (e.g., end-of-life or palliative care). The panel has attempted to evaluate the literature and best-practice guidelines to cover as many of these instances as possible, but not all possible clinical situations can be anticipated in such a broad undertaking. In these cases, the list can be used clinically not only for prescribing medications, but also for monitoring their effects in older adults. If a provider is not able to find an alternative and chooses to continue to use a drug on this list in an individual patient, designation of the medication as potentially inappropriate can serve as a reminder for close monitoring so that ADEs can be incorporated into the electronic health record and prevented or detected early. These criteria also underscore the importance of using a team approach to prescribing, of the use of nonpharmacological approaches, and of having economic and organizational incentives for this type of model.
These criteria have some limitations. First, even though older adults are the largest consumers of medication, they are often underrepresented in drug trials.33,35 Thus, using an evidence-based approach may underestimate some drug-related problems or lead to a weaker evidence grading. As stated previously, the intent of the updated 2012 AGS Beers Criteria, as an educational tool and quality measure, is to improve the care of older adults by reducing their exposure to PIMs. Second, it does not address other types of potential PIMs that are not unique to aging (e.g., dosing of primarily renally cleared medications, drug–drug interactions, therapeutic duplication). Third, it does not comprehensively address the needs of individuals receiving palliative and hospice care, in whom symptom control is often more important than avoiding the use of PIMs. Finally, the search strategies used might have missed some studies published in languages other than English and studies available in unpublished technical reports, white papers, or other “gray literature” sources.
Regardless, this update has many strengths, including the use of an evidence-based approach using the Institute of Medicine standards and the development of a partnership to regularly update the criteria. Thoughtful application of the criteria will allow for closer monitoring of drug use, application of real-time e-prescribing and interventions to decrease ADEs in older adults, and better patient outcomes. Regular updates will allow for the evidence for medications on the list to be assessed routinely, making it more relevant and sensitive to patient outcomes, with the goal of evaluating and managing drug use in older adults while considering the dynamic complexities of the healthcare system.
The decisions and content of the 2012 AGS Beers Criteria are those of the AGS and the panelists and are not necessarily those of the U.S. Department of Veterans Affairs.
Sue Radcliff, Independent Researcher, Denver, Colorado, provided research services. Susan E. Aiello, DVM, ELS, provided editorial services. Christine Campanelli and Elvy Ickowicz, MPH, provided additional research and administrative support. The development of this paper was supported in part by an unrestricted grant from the John A. Hartford Foundation.
The following organizations with special interest and expertise in the appropriate use of medications in older adults provided peer review of a preliminary draft of this guideline: American Academy of Family Physicians; American Academy of Nurse Practitioners; American Academy of Nursing; American College of Clinical Pharmacy; American College of Obstetrics and Gynecology; American College of Physicians; American College of Surgeons; American Medical Association; American Medical Directors Association; American Society of Anesthesiologists; American Society of Consultant Pharmacists; Centers for Medicare and Medicaid Services; Gerontological Advanced Practice Nurses Association; Gerontological Society of America; National Academies of Practice, Academy of Pharmacy; National Committee for Quality Assurance; Pharmacy Quality Alliance; Society for General Internal Medicine; Society of Hospital Medicine.
Dr. Beizer is an author and editor for LexiComp, Inc. She is on the Pharmacy and Therapeutics Committee for Part D at Medco Health Solutions. Dr. Brandt is on the Pharmacy and Therapeutics Committees at Omnicare and receives grants from Talyst (research grant), Econometrics (research grant), Health Resources and Services Administration (educational grant), and the State of Maryland Office of Health Care Quality (educational grant). Dr. Dubeau serves as a consultant for Pfizer, Inc. (urinary incontinence) and the New England Research Institute (nocturia). Dr. Fick is partially supported by the National Institute of Health (NIH) for National Institute of Nursing Research grants R01 NR011042 and R01NR012242. Dr. Hanlon is supported in part by National Institute on Aging grants and contracts (R01AG027017, P30AG024827, T32 AG021885, K07AG033174, R01AG034056), a National Institute of Nursing Research grant (R01 NR010135), and Agency for Healthcare Research and Quality grants (R01 HS017695, R01HS018721). Dr. Linnebur receives an honorarium for serving as a member of the Pharmacy and Therapeutics Committee for Colorado Access (a health plan serving indigent children and adults and Medicare members). Dr. Nau works for the PQA, which has received demonstration project grants from Pfizer, Inc., Merck & Co, Inc, sanofi-aventis, and GlaxoSmithKline. He also has held shares with CardinalHealth in the past 12 months. Dr. Semla receives honoraria from the AGS for his contribution as an author of Geriatrics at Your Fingertips and for serving as a Section Editor for the Journal of the American Geriatrics Society. He is a past President and Chair of the AGS Board of Directors. His spouse is an employee of Abbott Laboratories. He serves on the Omnicare Pharmacy and Therapeutics Committee. He is an author and editor for LexiComp, Inc.
Sponsor's Role: AGS staff participated in the final technical preparation and submission of the manuscript.
Conflict of Interest: Drs. Dombrowski, Flanagan, Hanlon, Hollmann, Rehm, Sandhu, and Steinman indicated no conflicts of interest.
Author Contributions: All panel members contributed to the concept, design, and preparation of the manuscript.
PANEL MEMBERS AND AFFILIATIONS The following individuals were members of the AGS Panel to update the 2012 AGS Beers Criteria: Donna Fick, PhD, RN, FGSA, FAAN, School of Nursing and College of Medicine, Department of Psychiatry, Pennsylvania State University, University Park, PA (co-chair); Todd Semla, PharmD, MS, BCPS, FCCP, AGSF, U.S. Department of Veterans Affairs National Pharmacy Benefits Management Services and Northwestern University, Chicago, IL (co-chair); Judith Beizer, PharmD, CGP, FASCP, St. Johns University, New York, NY; Nicole Brandt, PharmD, BCPP, CGP, University of Maryland, Baltimore, MD; Robert Dombrowski, PharmD, Centers for Medicare and Medicaid Services, Baltimore, MD (nonvoting member); Catherine E. DuBeau, MD, University of Massachusetts Medical School, Worcester, MA; Nina Flanagan, CRNP, CS-BC, Binghamton University, Dunmore, PA; Joseph Hanlon, PharmD, MS, BCPS, FASHP, FASCP, FGSA, AGSF, Department of Medicine (Geriatric Medicine) School of Medicine, University of Pittsburgh and Geriatric Education and Research and Clinical Center, Veterans Administration Health System, Pittsburgh, PA; Peter Hollmann, MD, AGSF, Blue Cross Blue Shield of Rhode Island, Cranston, RI; Sunny Linnebur, PharmD, FCCP, BCPS, CGP, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO; David Nau, PhD, RPh, CPHQ, Pharmacy Quality Alliance, Inc, Baltimore, MD (nonvoting member); Bob Rehm, National Committee for Quality Assurance, Washington, DC (nonvoting member); Satinderpal Sandhu, MD, MetroHealth Medical Center and Case Western Reserve University School of Medicine, Cleveland, OH; Michael Steinman, MD, University of California at San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, CA.