Eur J Clin Pharmacol (2007) 63:725–731DOI 10.1007/s00228-007-0324-2 Potentially inappropriate medications in the elderly:a French consensus panel list Marie-Laure Laroche & Jean-Pierre Charmes &Louis Merle Received: 15 February 2007 / Accepted: 9 May 2007 / Published online: 7 June 2007 Results The final list proposed 36 criteria applicable to Objective To evaluate drug-related problems in the elderly, people ≥75 years of age. Twenty-nine medications or various lists of potentially inappropriate medications have medication classes applied to all patients, and five criteria been published in North America. Unfortunately, these lists involved medications that should be avoided in specific are hardly applicable in France. The purpose of this study medical conditions. Twenty-five medications or medication was to establish a list of inappropriate medications for classes were considered with an unfavourable benefit/risk French elderly using the Delphi method.
ratio, one with a questionable efficacy and eight with both Method A two-round Delphi method was used to converge unfavourable benefit/risk ratio and questionable efficacy.
to an agreement between a pool of 15 experts from various Conclusion This expert consensus should provide prescrib- parts of France and from different backgrounds (five ers with an epidemiological tool, a guideline and a list of geriatricians, five pharmacologists, two pharmacists, two general practitioners, one pharmacoepidemiologist). Inround one, they were sent a questionnaire based on aliterature review listing medications and clinical situations.
Keywords Inappropriate medications . Elderly .
They were asked to comment on the potential inappropri- ateness of the criteria proposed using a 5-point Likert scale(from strong agreement to strong disagreement) and to suggest therapeutic alternatives and new criteria. In round two, the experts confirmed or cancelled their previous serotonin and noradrenaline reuptake inhibitor answers from the synthesis of the responses of round one.
After round two, a final list of potentially inappropriate Drug-related problems are a major public health issue, especially as many adverse drug reactions are considered Centre of Pharmacovigilance, University Hospital Dupuytren, preventable. Among these adverse effects, those linked to 87042 Limoges, Francee-mail: [email protected] unsuitable medications are of particular interest. Thesedrugs named IMs have an unfavourable benefit-to-risk ratio M.-L. Larochee-mail: [email protected] when safer or equally effective alternatives are available.
Therefore, IMs appear as a risk factor for preventable drug- related illnesses. Identifying these medications is of Department of Geriatrics, Hospital Rebeyrol, paramount importance when treating the elderly, who often 87042 Limoges, Francee-mail: [email protected] A way to establish a list of IMs in the elderly is the use of an expert consensus to develop explicit criteria when clinicalinformation is lacking. Explicit criteria have already been The Delphi method, developed by the Rand Corporation in proposed in the United States and Canada. In 1991, Beers the 1950s, is a research method allowing a consensus et al. developed the first list of criteria for determining IM use opinion to be reached among experts, using questionnaires, in nursing home residents []. In 1997, this criteria list was through an iterative process known as rounds ]. We used expanded so as to include drugs whose risk may outweigh two rounds in our study. The responses from the first round their benefit in all patients older than 65 years, whatever were collected and analysed; a revised questionnaire based their dwelling place A last updating of the Beers criteria on the results of this analysis was then submitted to the was published by Fick et al. in 2003 []. In Canada, McLeod same experts to converge to an agreement from the average et al. proposed another IM list because of a disagreement with some medications identified by Beers []. The Canadian The study was organised in six phases: (a) creation of the explicit criteria identified medications in the context of preliminary questionnaire of IMs from a literature review, drug–drug and drug–disease interactions. In these various (b) recruitment of the experts, (c) mailing of the round-one cases, the explicit criteria were obtained through a literature questionnaire, (d) analysis of the answers and creation of the review and a questionnaire evaluated by national experts new questionnaire, (e) mailing of this round-two question- involved in geriatric care, clinical pharmacology, psycho- naire based on round-one synthesis and (f) final analysis.
pharmacology, clinical pharmacy and ambulatory care.
A preliminary questionnaire about IM in the elderly was These North American criteria are not adapted to the constructed from the Beers lists (1991, 1997, 2003), the European situation. Availability of drugs, clinical practice, Canadian criteria (1997), the criteria adapted to French socioeconomic levels and health system regulations are practice (2001), and the guidelines of the French Medicine different from those prevailing in the United States and Agency (Agence Française de Sécurité Sanitaire des Canada and are even different between European countries Produits de Santé, AFFSaPS) on medication prescribing in ]. Nevertheless, we think the discrepancies between the elderly (June 2005) , , , ]. The questionnaire European countries are smaller than those that can be was composed of criteria that covered two categories: (a) identified when comparing North American and European medications or medication classes that should generally be practices. To our knowledge, up to now, no criteria for IMs avoided in the elderly as being either ineffective or prone to have been developed for European countries.
induce a risk when a safer alternative is available and (b) In France, an IM list derived from the 1997 Beers criteria medications that should be avoided in specific medical was elaborated in 2001 by nine French experts (five geri- atricians, four pharmacologists) and used in three studies Fifteen experts were invited to participate. The panel was Most of the Beers criteria were included in this list, composed of five pharmacologists, one pharmacoepidemi- except drugs not available in France, drugs necessitating ologist, five geriatricians, two pharmacists (one from dose information and drugs that should not be used in the hospital and one from community practice) and two general elderly under specific medical conditions. Three criteria practitioners with clinical geriatric qualification (one from were added: concomitant use of two (or more) nonsteroidal urban and one from rural areas). They were all selected anti-inflammatory drugs, concomitant use of two (or more) from different geographic parts of France. All the experts psychotropic drugs from the same therapeutic class and use accepted and participated in all the rounds of the study.
of any medications with anticholinergic properties other In April 2006, the round-one questionnaire was sent to than those listed by Beers. This list has some limits: lack the panel of experts together with information on how to fill of a consensus method, exclusion of some criteria (dose, in the forms. This preliminary questionnaire included 37 drugs in specific medical conditions), obsolescence of the criteria: 30 drugs or drug therapeutic classes independently list as a consequence of marketing and removal of drugs from the diagnoses and seven criteria linked to specific from the pharmaceutical market since 2001. Therefore, this medical conditions. Each criterion was to be evaluated by list is hardly usable in other pharmacoepidemiological the experts using a 5-point Likert scale [a score of 1 studies or in public health intervention for minimising meant a strong agreement on the inappropriateness, 3 meant drug-related problems. Besides, none of these lists (neither an equivocal opinion and 5 meant a strong disagreement North American nor that presently used in France) about inappropriateness. Experts were also invited to suggest suggested any alternative drugs to replace inappropriate safer alternative therapeutics and to add other criteria.
The responses were used to create the second question- The aim of this study was to establish a list of IMs for naire. Items with a median score of 1 or 2 were retained in the French elderly population using the Delphi method and the IM list; items with a median score of 4 or 5 were ex- to propose safer, effective alternatives.
cluded from the list. Items with a median score of 3 were resubmitted. A synthesis was elaborated, based on the ourable benefit-to-risk ratio and a questionable efficacy experts’ arguments and on the criteria suggested and then sent to the experts as round-two questionnaire.
In August 2006, the round-two questionnaire was sent to the panel of experts. This second questionnaire also included a synthetic table grouping the results of round-one scores, enabling the experts to compare their answers to We propose a list of explicit criteria for identifying the those of the members of their expert panel. The new criteria potentially IM use in the population 75 years of age and older and the criteria necessitating a consensus were evaluated in France. These criteria were identified from conditions with the same 5-point Likert scale. Experts confirmed the with, (a) an unfavourable benefit to risk ratio, (b) a ques- proposed therapeutic alternatives and indicated the reasons tionable efficacy or (c) an unfavourable benefit-to-risk ratio of criteria inappropriateness: (a) unfavourable benefit-to- together with a questionable efficacy. Safer therapeutic risk ratio, (b) questionable efficacy and (c) unfavourable alternatives were also indicated for each criterion.
benefit-to-risk ratio and questionable efficacy. At the end of This first French list of potentially IMs, based on a the last round, a final list of inappropriate drugs was consensus of experts, regrouped the opinion of practitioners retained. In this second round, experts also indicated from commonly involved in the management of drugs given to what age this list of IMs could be applied.
elderly people. The geographical dispersion and the variouspractice modes give a large overview of medical andpharmaceutical practices in France. The French experts considered that the list could be applicable in the thepopulation aged 75 years and older, as from this age on, The expert panel considered this list was applicable to pharmacokinetic and pharmacodynamic changes are signif- people 75 years of age and older. Younger elderly patients icant enough to markedly alter the response to medications were considered as quite similar to middle-aged adults.
]. The French list of potential IMs proposed here retains In the first round, 37 criteria were submitted to the panel some of the Beers criteria. Several drugs or therapeutic drug of experts. Thirty criteria were considered by these experts classes were not selected, as they are not available on the as inappropriate in the elderly (median score: 1 or 2). One French market (pentazocine, trimethobenzamide, fluraze- criterion was not selected: amiodarone (median score: 4).
pam, meperidine, oorphenadrine, guanadrel, isoxsuprine, For six criteria, no consensus was obtained, so they were to doxazosin, thioridazine, mesoridazine, ethacrynic acid, be submitted again during the second round of evaluation desiccated thyroid) or are no longer available, as they are (dextropropoxyphene-paracetamol, fluoxetine, long-term judged harmful and ineffective, such as barbiturates (except prescription of NSAIDs, long-term prescription of NSAIDs phenobarbital). Several criteria were not considered for the for patients with a history of hypertension, long-term consensus, as they differed from common medical practi- prescription of NSAIDs for patients with a history of renal ces: unopposed estrogens, for instance, are not prescribed in failure and antispasmodic drugs with anticholinergic prop- France without association with progesterone in the erties). Three criteria were proposed by the experts treatment of menopause. Phenylbutazone, dropped from (association of drugs with anticholinergic properties, con- the 2003 Beers list, was integrated in the French list comitant use of drugs with anticholinergic properties because of the serious haematological effects it could together with anticholinesterase drugs and myorelaxants induce. Among the criteria added in the 2003 Beers list, two drugs were not judged as inappropriate by French After the issue of the second round of evaluation, among experts: fluoxetine, which was not considered as more 39 criteria, five were definitely eliminated by the French prone to induce problems than any other selective serotonin experts (dextropropoxyphene-paracetamol, fluoxetine, reuptake inhibitor, and amiodarone, which was judged as long-term prescription of NSAIDs, long-term prescription effective and as susceptible to inducing adverse effects as of NSAIDs for patients with a history of hypertension and do the other available antiarrhythmics [Conversely, the long-term prescription of NSAIDs for patients with a French experts, like their North American counterparts, history of renal failure). The final list contained 34 criteria: considered nitrofurantoin, short-acting nifedipine and stim- 29 medications or medication classes to be used in all older ulant laxatives as inappropriate in the elderly. Lastly, the people and five criteria related to medications that should obtained consensus allowed confirmation of criteria added be avoided in specific medical conditions (Table ). Among in the previous list and adapted to French practice: these 34 criteria, 25 were considered inappropriate as their concomitant use of two (or more) nonsteroidal anti- benefit-to-risk ratio was unfavourable, 1 was considered inflammatory drugs, concomitant use of two (or more) with questionable efficacy and eight with both an unfav- psychotropic drugs from the same therapeutic class and use of any medications with anticholinergic properties other The Delphi method is a consensus technique used and validated in various health domains such as nursing, clinical practice or education , This technique has some limitations. The reliance on intuitive judgements is obviously not an accurate method and depends mostly on the panel of experts chosen. Every expert would summarise their experience in a single answer. However, a complex situation such as the study of the appropriateness of drugs given to elderly patients with multiple adverse-effect- facilitating factors can hardly be solved. Participants could change opinions between rounds, which may introducesome biased responses, as the results of the first round weremade available to all participants who could thus compare their opinions to that expressed by their group. Experts were consulted separately and were not able to debate; this would allow for more clear-cut opinions but would complicate the path towards a consensus. Nevertheless, the Delphi method allows experts to express their opinions independently and confidentially without the pressures that may occur during a face-to-face meeting [Finally, the consensus obtained is the average of the experts due to the convergence of opinions throughout the The Delphi method allowed the proposal of explicit criteria for assessing prescribing quality to older people.
However, explicit criteria tools are stringent and do not take into account the clinical context of prescribing ]. For instance, the NSAIDs criterion was much debated between experts with respect to dose, administration duration, continuity or not of treatment, co-prescriptions, age andrenal and cardiovascular functions. Finally, NSAIDs were not classified as inappropriate, but the use of these drugs with neither adaptation to the clinical condition nor surveillance was considered harmful and inappropriate.
Therefore, for several criteria, the French list encom- passes some clinical conditions, especially those most frequently encountered in geriatric practice. However, their number is limited, as considering the clinical condition of the patient together with the drugs given adds complexity and hampers the epidemiological analysis. As Beers emphasised, these criteria do not allow the identification of all cases of the use of potentially IMs Only the main ones are mentioned in this study. They are based on expert opinions and are not drawn from an evidence-based This list of criteria is a general guide for assessing the potential inappropriateness of medications. Nevertheless, for a given patient, a benefit-to-risk ratio has also to be assessed due to evaluation of the clinical condition, co- morbidities, functional status, drugs received and progno- sis. This set of criteria should not be used as a substitute for the clinical evaluation, which could lead reasonably, at 4. McLeod PJ, Huang AR, Tamblyn RM, Gayton DC (1997) times, to the appropriate prescription of supposedly Defining inappropriate practices in prescribing for elderly people:a national consensus panel. Can Med Assoc J 156:385–391 inappropriate and second-choice drugs such as indometha- 5. Fialova D, Topinkova E, Gambassi G, Finne-Soveri H, Jonsson PV, cin, tricyclic antidepressants, or antipsychotics with anti- Carpenter I, Schroll M, Onder G, Sorbye LW, Wagner C, Reissigova J, Bernabei R, AdHOC Project Research Group This list should not be seen by people without adequate (2005) Potentially inappropriate medication use among elderlyhome care patients in Europe. JAMA 293:1348–1358 clinical expertise as an absolute prohibition against pre- 6. Gallagher P, Barry P, O’Mahony D (2007) Inappropriate prescrib- scribing certain medications [Care should also be taken ing in the elderly. J Clin Pharm Ther 32: 113–121 to prevent this list from being considered solely as an 7. Lechevallier-Michel N, Gautier-Bertrand M, Alperovitch A, Berr C, opposable reference for economic purposes, for instance, by Belmin J, Legrain S, Saint-Jean O, Tavernier B, Dartigues JF,Fourrier-Reglat A, The 3C Study Group (2005) Frequency and risk the social security system: its first aim is epidemiological; factors of potentially inappropriate medication use in a community- its second aim is the supply of clinical guidelines. It is not dwelling elderly population: results from the 3C study. Eur J Clin devised for the economic regulation of care but can, however, help reduce the cost of drug misuse.
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