Could we also stop this one? Deprescribing Inappropriate Medications in Western Switzerland’s Nursing Homes

Thesis

Reference

Could we also stop this one? Deprescribing Inappropriate Medications in Western Switzerland's Nursing Homes

CATEAU, Damien

Abstract

Polypharmacy and the use of potentially inappropriate medications (PIMs) are frequent prescribing problems among nursing home (NH) residents. Deprescribing has recently emerged as a powerful tool to reduce both problems. The Opportunities and Limits to Deprescribing in Nursing Homes (OLD-NH) trialled two complementary deprescribing interventions in the NHs of Vaud and Fribourg, one at the NH level (QC-DeMo), the other at the resident level (IDeI). Fifty-six NHs took part in the QC-DeMo trial, with 27 randomised to the intervention group. There was a strong trend towards a reduction in PIMs use in the intervention group, and the use of some PIMs classes decreased significantly. The IDeI trial recruited 58 NH residents, and showed that this intervention successfully reduced the doses of PIMs used. No adverse effects were seen on death, hospitalisations, falls, and physical restraints use, but a trend towards a decrease in quality of life was noted.

CATEAU, Damien. Could we also stop this one? Deprescribing Inappropriate

Medications in Western Switzerland's Nursing Homes . Thèse de doctorat : Univ. Genève, 2020, no. Sc. Vie 90

DOI : 10.13097/archive-ouverte/unige:149510 URN : urn:nbn:ch:unige-1495105

Available at:

http://archive-ouverte.unige.ch/unige:149510

Disclaimer: layout of this document may differ from the published version.

UNIVERSITÉ DE GENÈVE FACULTÉ DES SCIENCES Section des sciences pharmaceutiques Professeur O. Bugnon

Could we also stop this one? Deprescribing Inappropriate Medications in Western Switzerland’s Nursing Homes

THÈSE

présentée aux Facultés de médecine et des sciences de l’Université de Genève pour obtenir le grade de Docteur ès sciences en sciences de la vie,

mention Sciences pharmaceutiques

par

Damien CATEAU

de Thônex (GE)

Thèse N

90

GENÈVE

2020

Remerciements

Cette thèse n’aurait, évidemment, pas été possible ans le soutien et la participation de nombreuses personnes.

J’aimerais tout d’abord remercier tous les participants aux différentes études qui ont composé cette thèse et, plus largement, le projet OLD-NH. Merci à tous les médecins, infirmières et infirmiers, pharmaciennes et pharmaciens qui ont participé aux focus-groups et séances de travail Un merci encore plus grand à tous ceux qui se sont engagés dans les deux essais cliniques QC-DeMo et IDeI. Parmi tous ceux-là, je remercie tout spécialement les pharmaciennes et pharmacien de l’essai IDeI, qui se sont lancés avec courage dans une activité nouvelle pour la grande majorité d’entre eux, ainsi que tous les intervenants dans les EMS fribourgeois, qui ont persévéré dans leur engagement malgré l’abandon de leur modèle d’assistance pharmaceutique en 2018. J’espère que ce modèle redémarrera un jour !

Je remercie également toutes les organisations professionnelles qui se sont engagées pour que le projet OLD-NH se concrétise : pharmaSuisse, la Société Vaudoise de Pharmacie, la Société des Pharmaciens fribourgeois, Héviva, l’AFIPA/VFA, le GMEMS, en la personne de la Dresse Tosca Bizzozero, et le Service de la Santé Publique du Canton de Vaud, au travers de Mme Marie- Christine Grouzmann. Merci également à Martine pour m’avoir donné la possibilité de l’assister durant les formations d0assistance pharmaceutique ; ça a été une expérience formatrice, et je suis sûr qu’on aura encore l’occasion de collaborer autour de ça (ou d’autres choses), Mme la Présidente !

Merci à toute l’équipe recherche pour son accueil, sa bienveillance et son soutient pendant ces cinq ans : Clémence, Jenny, Aline, Sophie, Pierluigi, Noura, Patricia, Marie, Stephanie, Élodie, Gordana, Gwenaëlle, Jérôme, Susan, ça a été cinq belles années passées avec vous. Merci pour les pauses-café, les pauses-gâteau, les pauses-chocolat, et toutes les pauses-discute.

À part l’équipe d’assistance pharmaceutique, j’ai assez peu côtoyé le reste de l’équipe de la pharmacie, mais je m’y suis toujours senti bien accueilli (et bien nourri !) ; merci à vous pour votre chaleur humaine. De nombreux civilistes ou stagiaires à la pharmacie d’Unisanté ont aussi, de près ou de loin, contribué à la réalisation de cette thèse : Arnaud, Paul, Simona, Olivier, Jérôme, et j’en oublie. Merci à vous tous ! Merci également à Laure, sans qui la formation QC-DeMo n’aurait pas vu le jour, et à Pierre-Olivier, sans qui toutes ces sessions de formation auraient été bien plus ternes.

À toutes les équipes des pharmacies de Begnins, de la Harpe et de l’Ile : merci pour votre soutien et votre intérêt pendant ces 5 ans. Merci à Florane et Karine d’avoir été flexibles dans leurs demandes de remplacements, et compréhensives durant ces derniers mois.

Tant qu’on parle de flexibilité, merci à mes parents et à mes beaux-parents pour leur soutien durant ces 5 ans, et pour l’immense aide que vous nous avez apporté, à Claudia et moi, avec Lisa et Lars. Merci maman, merci papa pour vos encouragements à démarrer cette thèse, qui m’ont aidé à sauter le pas ; merci à Dorcas et Stefan pour votre intérêt, même s’il était parfois difficile de communiquer sur comment se passait mon travail (Wie sagt mann das ?).

Il me reste à remercier quatre personnes sans qui rien de tout ça n’aurait été possible ; difficile de choisir par qui commencer, alors allons-y par ordre alphabétique des prénoms :

Anne, merci pour ton encadrement incroyable durant toute cette aventure. Merci pour tes avertissement (yep, la deuxième année, c’est la shit), et merci de m’avoir laissé la liberté et l’autonomie dont j’ai besoin. Merci d’avoir partagé tes doutes, tes frustrations et ta surcharge chronique de travail, mais aussi ta motivation, ton amour de la science bien faite, et ta persévérance à toute épreuve. Merci aussi d’avoir courageusement porté notre équipe de recherche sur tes épaules depuis le départ d’Olivier.

Si Christophe est le best chef ever, tu es la best supervisor ever.

Claudia, merci tout simplement pour ton amour et ta compréhension durant ces cinq ans. Tu étais là quand ça allait, quand ça n’allait pas, et quand je ne savais même plus si ça allait ou pas. Tu as accepté que je me lance dans cette aventure, même si ça diminuait drastiquement tes chances de pouvoir un jour vivre simplement avec ma carte de crédit. J’espère que je pourrais être autant là pour toi pendant ta prochaine aventure que tu l’as été pour moi pendant la mienne. Je t’aime.

Christophe : best chef ever ; que dire de plus ? Merci de m’avoir ouvert les yeux sur tout ce qu’il était possible de faire en tant que pharmacien ; sans toi, j’aurais été m’enterrer dans un labo… Merci de m’avoir, toi aussi, laissé la liberté dont j’ai besoin, de m’avoir permis de me former, et de m’avoir (quasi littéralement) laissé choisir ce que je voulais continuer à faire pour toi pendant ma thèse. Merci parce que, au fil du temps, tu es devenu bien plus qu’un patron. J’espère qu’on va pouvoir continuer à travailler longtemps ensemble !

Olivier, tu as été l’un des premiers à m’offrir une perspective sur la vie réelle, en dehors des labos, des systèmes physiologiques, et des raisonnements de pharmacologie. Merci pour ton enthousiasme et ta foi inébranlable en l’impact positif que nous pouvons avoir, en tant que pharmacien, sur le monde qui nous entoure. Il y a plein de sujets sur lesquels on n’était pas d’accord, mais au final, on se retrouve sur l’essentiel : on peut faire changer les choses pour le mieux. Grâce à ton offre de démarrer cette thèse, j’ai découvert de nouveaux horizons, et je regrette que tu ne sois pas avec nous pour la voir arriver à son terme. So long, Professeur Filet Mignon !

Table of contents

Abstract ... i

Résumé ... ii

Introduction ... 1

General context ... 1

Swiss context ... 4

The OLD-NH project ...7

First chapter: Epidemiologic analysis of the use of Potentially Inappropriate Medications in Swiss NHs ... 13

Summary ... 13

Evolution of potentially inappropriate medication use in NHs: Retrospective analysis of drug consumption data ... 15

Supplementary material ... 21

Second chapter: designing and planning the interventions ...25

Summary ...25

Deprescribing in NHs: Protocol for nested, randomised controlled hybrid trials of deprescribing interventions ...27

Third chapter: results of the Quality Circle-Deprescribing Module trial... 36

Summary ... 36

Contribution of the authors ... 36

Effects of an interprofessional Quality Circle-Deprescribing Module in Swiss NHs: a randomized controlled trial ...38

Supplementary material ... 51

Fourth chapter: results of the Individual Deprescribing Intervention trial ...54

Summary ...54

Effects of an interprofessional deprescribing intervention in Swiss NHs: the IDeI randomized controlled trial. ... 56

Supplementary material ... 66

Discussion and conclusion... 68

Synthesis of the results... 68

Results in light of other efforts to improve drug and medical care use ... 69

Core outcome sets ... 71

Strengths, limitations, and potential improvements ... 71

Perspectives for future research ... 73

Conclusion ...74

Annexes ...78

Abstract

Polypharmacy, the concurrent use of multiple drugs, and the use of potentially inappropriate medications (PIMs), drugs with negative risk/benefit ratio in older people, are frequent among nursing home (NHs) residents. In Switzerland, it is estimated that at least 50% of them are exposed to one of these two problems. Deprescribing, “the process of withdrawal of an inappropriate medication […] with the goal of managing polypharmacy and improving outcomes”, has recently emerged as a powerful tool to reduce both polypharmacy and the use of PIMs.

In the NHs of Vaud and Fribourg, the collaboration between nurses, physicians, and pharmacists are structured by an Integrated Pharmacy Service (IPS) centred on a quality circle methodology. The existence of this IPS provided a favourable context to trial deprescribing interventions in these NHs. The Opportunities and Limits to Deprescribing in Nursing Homes (OLD-NH) project was launched in 2016 to trial two complementary deprescribing interventions targeting the use of PIMs, one at the NH level, the other at the resident level.

Before trialling the two interventions, an epidemiologic analysis of the use of PIMs in the NHs of Vaud and Fribourg was performed. This analysis used the data routinely collected for the monitoring of the IPS. PIMs were identified by combining two validated lists, the Norwegian General Practice-Nursing Home (NORGEP-NH) criteria, and the 2015 American Geriatrics Association Beers’ list. PIMs use was quantified using the WHO’s Defined Daily Dose (DDD) system, which is widely used for pharmacoepidemiologic purposes. Data from 166 NHs were analysed from 2014 to 2018. Polypharmacy was high at baseline, with NHs delivering a median of 7.4 DDD per average resident and per day (DDD/res); 2.4 of these DDD/res could be considered potentially inappropriate. In the five years analysed, overall polypharmacy increased (+0.087 DDD/res every year, p=0.01), but PIMs use decreased (-0.033 DDD/res every year). While statistically significant, this reduction is probably not clinically meaningful, especially considered the high baseline level.

The first intervention to be trialled was called Quality Circle – Deprescribing Module (QC-DeMo). It consisted of a quality circle session gathering a NH’s pharmacist, nurses, and physicians, and resulting in the implementation of a local deprescribing consensus targeting specific classes of PIMs. Its effects were evaluated on the use of PIMs, using the methodology developed for the epidemiological analysis, and on patient safety outcomes such as mortality, hospitalisations, use of physical restraints, and falls.

Fifty-six NHs took part in the QC-DeMo trial, with 27 randomised to the intervention group. There was a strong trend towards a reduction in PIMs use in the intervention group (-0.183 DDD/res, CI95 [-0.392; +0.025], p=0.083), and the use of proton pump inhibitors was significantly reduced (-0.067 DDD/res, CI95 [-0.123; -0.010], p=0.022). The intervention had no effects on falls and the use of physical restraints; for hospitalisations and mortality, the results were conflicting: as strong interaction was seen between the allocation group and mission (geriatric or psycho-geriatric) of the NH. In the psychogeriatric NHs of the intervention group, mortality was significantly reduced, while hospitalisations were significantly increased; no such effects were seen for the geriatric mission.

The trial for the resident-level intervention took place in seven NHs of the intervention group in the QC-DeMo trial. The Individual Deprescribing Intervention (IDeI) trial recruited 62 residents; the intervention consisted of a medication review, followed by the drafting of an individual treatment modification plan by the NH physician, nurses, and pharmacist and its implementation. Its effects were evaluated on the number and dose of PIMs, participants’ quality of life (QoL), and on the same safety outcomes than for QC-DeMo.

The IDeI did not reduce the number of PIMs prescribed to the participants; however, it significantly decreased their dose (incidence rate ratio 0.763, CI95 [0.594; 0.979], p=0.033), in particular for chronic drugs (IRR 0.716, CI95 [0.546; 0.938], p=0.015). No adverse effects were seen on death, hospitalisations, falls, and physical restraints use, but a strong trend towards a decrease in QoL was seen in the intervention group.

The epidemiologic analysis showed that PIMs were largely used in the NHs of Fribourg and Vaud, and that their use did not meaningfully decrease since 2014. The clinical trials confirmed that deprescribing interventions can reduce the use of PIMs in NHs, although doing so may have a detrimental effect on some crucial aspects of residents’ well-being. Further developing these interventions seem worthwhile, and they may be adapted to other settings than the NH, but particular attention must be paid to patient safety when doing so.

Résumé

La polypharmacie, l'utilisation simultanée de plusieurs médicaments, et l'utilisation de médicaments potentiellement inappropriés (MPI), qui présentent un rapport bénéfice/risque négatif chez les personnes âgées, sont fréquents chez les résidents d’établissements médico-sociaux (EMS). En Suisse, on estime qu'au moins 50 % d'entre eux sont exposés à l'un de ces deux problèmes. La déprescription, "le processus de retrait d'un médicament inapproprié [...] dans le but de réduire la polypharmacie et d'améliorer les résultats de santé", est récemment apparue comme un outil puissant pour réduire à la fois la polypharmacie et l'utilisation des MPI.

Dans les EMS de Vaud et de Fribourg, la collaboration entre les infirmières, les médecins et les pharmaciens est structurée par un programme d’assistance pharmaceutique (PAP) centré sur une méthodologie de cercle de qualité. L'existence de ce PAP a créé un contexte favorable à l’étude d’interventions de déprescription dans ces EMS. Le projet "Opportunities and Limits to Deprescribing in Nursing Homes" (OLD-NH) a été lancé en 2016 pour tester deux interventions complémentaires de déprescription ciblant l'utilisation des MPI, l'une au niveau des EMS, l'autre au niveau de leurs résidents.

Avant de tester les deux interventions, une analyse épidémiologique de l'utilisation des MPI dans les EMS de Vaud et de Fribourg a été réalisée. Cette analyse a utilisé les données récoltées en routine pour le suivi des PAP. Les MPI ont été identifiées en combinant deux listes validées, les critères du Norwegian General Practice-Nursing Home (NORGEP-NH) et la liste de Beers 2015 de l'American Geriatrics Association. L'utilisation des MPI a été quantifiée en recourant au système de Defined Daily Dose (DDD) de l'OMS, qui est largement utilisé en pharmacoépidémiologie. Les données de 2014 à 2018 de 166 EMS ont été analysées. La polypharmacie était élevée en 2014, les EMS délivrant une médiane de 7.4 DDD par résident moyen et par jour (DDD/res); 2.4 de ces DDD/res étaient potentiellement inappropriés. Au cours des cinq années analysées, la polypharmacie a globalement augmenté (+0.087 DDD/res chaque année, p=0.01), mais l'utilisation des MPI a diminué (-0.033 DDD/res chaque année, p=0.001)). Bien que statistiquement significative, cette réduction n'est probablement pas cliniquement pertinente, étant donnée l’utilisation initiale élevée de MPI.

La première intervention à être testée, intitulée Quality Circle - Deprescribing Module (QC-DeMo), consistait en une session de cercle de qualité réunissant pharmacien, infirmières et médecins de l’EMS, et a abouti à la création et l’implémentation d'un consensus local de déprescription ciblant des classes spécifiques de MPI. Ses effets ont été évalués sur l'utilisation des MPI selon la méthodologie développée pour l'analyse épidémiologique, et sur des aspects cruciaux de sécurité des patients : la mortalité, les hospitalisations, l’utilisation de mesures de contrainte, et les chutes.

Cinquante-six EMS ont participé à l'essai QC-DeMo, dont 27 randomisés dans le groupe intervention. Une forte tendance à la réduction de l'utilisation des MPI a été constatée dans le groupe intervention (-0.183 DDD/res, IC95 [-0.392 ; +0.025], p=0.083), et l'utilisation des inhibiteurs de la pompe à protons a été réduite de manière significative (-0.067 DDD/res, IC95 [-0.123 ; -0.010], p=0.022). L'intervention n'a pas eu d'effets néfastes sur les chutes et l'utilisation de mesures de contrainte ; pour les hospitalisations et la mortalité, les résultats sont contradictoires : une forte interaction a été observée entre le groupe d'allocation et la mission (gériatrique ou psycho-gériatrique) de l’EMS. Dans les EMS psychogériatriques du groupe intervention, la mortalité a été significativement réduite, tandis que les jours d’hospitalisation ont été significativement augmentés ; aucun effet de ce type n'a été observé pour la mission gériatrique.

L'intervention au niveau des résidents a été testée dans sept EMS alloués au groupe intervention de l'essai QC-DeMo. L'essai IDeI (Individual Deprescribing Intervention) a recruté 62 résidents ; l'intervention consistait en une analyse de médication, suivie de la mise en œuvre d'un plan de modification du traitement individuel défini par le médecin, les infirmières et le pharmacien de l’EMS. Ses effets ont été évalués sur le nombre et la dose des MPI, la qualité de vie des participants, et sur les mêmes résultats de sécurité que pour QC-DeMo.

Même si l’intervention individuelle de déprescription n'a pas diminué le nombre de MPI prescrits, elle a réduit de manière significative les doses utilisées (incidence rate ratio 0.763, IC95 [0.594 ; 0.979], p=0.033), en particulier pour les médicaments chroniques (IRR 0.716, IC95 [0.546 ; 0.938], p=0.015). Aucun effet néfaste n'a été observé sur les décès, les hospitalisations, les chutes et l'utilisation de moyens de contention physique, mais une forte tendance à la baisse de la qualité de vie a été observée dans le groupe d'intervention.

L’analyse épidémiologique a montré que les MPI étaient couramment utilisées dans les EMS vaudois et fribourgeois, et que leur usage n’avait pas substantiellement diminué depuis 2014. Les deux essais cliniques ont confirmé que les interventions de déprescription testées peuvent réduire l'utilisation de MPI dans les EMS, bien que cela puisse potentiellement diminuer le bien-être des résidents. Il semble pertinent de développer davantage ces interventions, et de les adapter à d'autres contextes que celui des EMS, mais il sera nécessaire d’accorder une attention particulière à la sécurité des patients.

Introduction

General context

There is such a thing as being too-well fed.

In the past 300 years, agriculture underwent a dramatic increase in productivity, stemming from multiple factors like greater automation and a better comprehension of plant and animal biology, and resulting in a an enormous improvement in available calories and a fantastic diminution in hunger throughout the world.¹ Even in the last 30 years, progress has been staggering: the number of people who are undernourished fell by 20% between 1991 and 2017.² In Angola, the most dramatic example of improvement, from 70% in 2000, the prevalence of undernourishment fell to just over 30% in 2012.² This positive evolution did not, however, come without bringing new issues: as the share of population being undernourished fell, the proportion of mis- or over- nourished people rose dramatically.

Medicine in general and drugs in particular have undergone a similarly spectacular evolution: their development in the past centuries contributed to incredible improvements in areas such as life expectancy and deaths due to infectious disease. But this progress also enabled new issues to emerge, like the overuse of medicine, drug misuse, and drug overuse. Being too-well fed is a thing, and so is being too-well medicated.

Population ageing

Life expectancy rose dramatically in the last two centuries:

from a global average of 29 years in 1800, life expectancy at birth rose to an average of 72 years in 2015, and over 80 years in many countries.³ Some populations experienced a decrease in life expectancy in the past decades, such as in post-Soviet eastern European countries or, more recently, in the United States following the opioids epidemic of the 2010s, but the overall global trend is towards increase.

This evolution implies that the population has aged:

people 65 years and older were 8% of Europe’s population in 1950, and 18% in 2015; this proportion is expected to rise to 28% in 2050, and over 30% in 2100.⁴ Not all regions or countries have experienced such a dramatic evolution yet, but the UN projects that 22% of the world population will be over 65 in 2100.⁵

All these years of life gained are not, regrettably, years in good health: increases in life expectancy have been followed by increases in years lived with significant disability or disease. In China, life expectancy increased from 67 years to 76 years between 1990 and 2016, and life with disease or disability from 7.1 to 8.5 years.³ Data from the Global Burden of Disease Study 2017 show that healthy life expectancy grows more slowly that total life expectancy in many developed countries: 57% of life years gained in Canada between 1990 and 2017 were years in poor health; in Sweden, this proportion was 68%.⁶

Switzerland fares very similarly to its peers in the OECD (Organisation for Economic Co-operation and Development), a group of mostly developed countries: its share of population over 65, 18% in 2015, is expected to reach 29% in 2050 and over 30% in 2100. ⁴ Both its total life expectancy at birth (86 years for females, 82 for males) and healthy life expectancy at birth (73 and 71 years) are slightly above the OECD average.⁶ A typical 65 years old female in 2017 could expect to live for 23 more years, and a typical male 20 years, but only 17, respectively 15, of those would be without a significant burden of disease.⁶ The prolongation of life with disease or disability will increase the need for long-term care in most developed countries; how this care will be distributed between the community (ageing-in-place) and institutions is still unknown but, after years of decrease, the proportion of the population living in nursing homes (NH) is expected to rise in the next decades.⁷

Multimorbidity

These years of life in poor health are sometimes caused by isolated diseases or disabilities, but more often by combinations of many conditions, chronic and acute. This phenomenon, multimorbidity, is hard to pinpoint, as its definition is not universally agreed on.⁸ Hence, estimates of its prevalence vary wildly: for people aged 75 years, Fortin and colleagues retrieved estimates ranging from 13% to 72% in the general population, and from 4% to 99%

in primary care. ⁹ What is certain is that multimorbidity increases with age: all studies that reported it in different age groups found a similar trend, albeit with variations in the absolute estimates.⁹

In Switzerland, Pache and colleagues found a prevalence of multimorbidity ranging from 23% to 56% in the general population, depending on the definition. Estimates were consistently higher in persons aged 65 years and older, ranging from 38% to 70%.¹⁰ In a subsequent study, Gnädinger and colleagues found that nearly 80% of patients between 61 and 70 years old consulting a GP had two or more chronic conditions, and close to 95% of patients between 81 and 90.¹¹

Taking care of this ageing, multimorbid population is proving more and more challenging for physicians and the healthcare system as a whole, as health systems remain focused on single diseases (e.g. osteoporosis, heart failure, or depression).^12-14

A frequently-cited problematic element of current healthcare are treatment guidelines, which frequently fail to account for the polymorbid status of patients.¹⁵ Additionally, most guidelines are becoming larger and more in-depth, and so harder to put into practice: the 57 pages (excluding references) 2013 European Society of Hypertension guideline ¹⁶ was updated in 2018 to 79 pages.¹⁷ The 2019 Standards of Medical Care in

Diabetes, from the American Diabetes Association, occupied a full 186 pages of the Diabetes Care journal.¹⁸ These guidelines may also not be suitable for older adults, as they are predominantly based on the results of clinical trials that excluded older, frail or multimorbid participants.¹⁹

Polypharmacy

Unsurprisingly, suffering from multiple conditions is associated with negative outcomes, such as lower quality of life²⁰ or a higher risk of frailty.²¹ Treating these conditions, or preventing or slowing their evolution, is therefore one of the main goals of modern medicine, and drugs are frequently used to reach it; another corollary of multimorbidity is therefore polypharmacy.

Classically defined as taking five or more drugs concurrently, polypharmacy has become a subject of great interest in the past two decades: the number of publications on this subject increased more than tenfold between 2000 and 2019 (source: PubMed.gov). It is widely sought of as unsafe, as the risk of drug-drug interactions increases exponentially with each new drug added to a patient’s regimen, but definitive evidence of harm is lacking. Polypharmacy has been associated with negative health outcomes, such as falls, hospitalisations, and mortality, but the causality is hard to elucidate, as confounding factors are manifold.^{22, 23} It is also, this time perhaps surprisingly, conducive to under-treatment, as clinicians are reluctant to prescribe new drugs to already heavily-medicated patients.²⁴ Despite all this interest, the prevalence of polypharmacy, like multimorbidity, remains uncertain, as studies used different cut-off points and included different populations;²⁵ its prevalence in Switzerland, for example, was estimated at between 12%, in a cohort of adults aged 40 to 81 years, and 26%, in an European study focused on adults over 65.^{26, 27} In residential long-term care worldwide, the prevalence ranged from 65% to 91% of residents, depending on the cut- off.²⁵ Despite these uncertainties around its prevalence and the regional variations, polypharmacy is thought to be increasing worldwide: longitudinal studies that used consistent measures of polypharmacy over time all found an increase in its prevalence, albeit at different rates.²⁸ Despite these concerns, polypharmacy is not always synonymous with poor prescribing, as the use of multiple medication is sometimes the best available option: Payne and colleagues showed that, while a high number of drugs was associated with a higher risk of unplanned hospitalisation, this effect was greatly reduced in patients with multiple conditions.²⁹ A clear number of drugs below which combinations are safe may not even exist: Viktil and colleagues showed that the risk of drug-related problems increases quasi linearly with the number of drugs used, starting with the first one.³⁰ Therefore, the concern is increasingly not only the number of drugs a patient receives, but how they contribute to one’s well-being and health, i.e. are they appropriate.

Potentially inappropriate medications

The appropriateness of some widely-used drugs in certain populations has been questioned for quite some time: in 1977, Anthony Covert and colleagues noted that the use of antipsychotics in NH residents was “fraught with potential abuse”, and that they should be used sparsely to control “socially disruptive behaviors”.³¹ A subsequent study found that nearly 10% of NH residents in the United States received antipsychotics on a regular basis, denoting misuse of these drugs.³²

These concerns were formalised in 1991 with the first consensus-based list of potentially inappropriate medications (PIMs), commonly known as the Beers’ list, following the name of its author, Mark Beers.³³ The 30 drugs included in this first list were considered inappropriate for NH residents because of their direct negative consequences. Nineteen of them should generally not be used, and some dosage, duration or frequencies should be avoided in the other eleven.

The 1991 Beers’ list was focused on NH residents, but PIMs have since been recognised as a major problem in geriatrics as a whole, and multiple lists have since been published, to account for differences in regional or national prescribing practices; a 2014 systematic review identified 46 lists, and more have been published since.³⁴ The concept of inappropriate medication has expanded to include concerns beside direct harm from single drugs:

some recent PIMs lists include common drug combinations and preventive drugs whose time to benefit is considered too long for some populations.^{35, 36} Unsurprisingly, given the multitude of lists available, drawing a precise picture of PIMs use is no easy task:

multiple systematic reviews have reported rates of use between 5% and 83%,^{37, 38} indicating either wide variations between national practices, inconsistence between the different tools and studies, or both. Morin and colleagues estimated the point prevalence for NH residents to be higher in Europe (49%) than in North America (27%), although the tools used to identify PIMs were very different.³⁸ Beside the number of drugs used, which naturally increases the probability of PIM use, the factors influencing the use of PIMs are not well known: different studies reported positive, negative, or no association with age, for example.^{38, 39}

The exact drugs considered inappropriate differ between lists, but the overall categories are fairly consistent: the long-term use of benzodiazepines, the use of antipsychotics for the management of behavioural and psychological symptoms of dementia, drugs inducing a high risk of hypoglycaemia, and drugs with anticholinergic properties are universally considered inappropriate. While the association of PIMs use with the most crucial clinical outcome, mortality, is still lacking,^{40, 41} there is mounting evidence that inappropriate drugs are associated with negative outcomes, such as higher hospitalisation risk, adverse drug reactions, or a lower quality of life.⁴¹

Some interventions, particularly pharmacist-led medication reviews, have successfully reduced the use of PIMs, but it is not known whether this meaningfully improves clinical outcomes for patients.^{42, 43}

Medicine overuse

Concerns about polypharmacy and the use of PIMs echo similar reflexions in many medical fields about, broadly, the overuse of medicine.⁴⁴ These reflexions are not knew in any way: see, for a not too recent example, Ivan Illich’s 1975 Medical nemesis, whose opening sentence is “The medical establishment has become a major threat to health.”⁴⁵ These qualms about the overuse of medicine have, however, become more prominent in the last 20 years:⁴⁴ the BMJ, for example, published a special issue in 2002 titled “Too much medicine?” (“Almost certainly”, stated the lead of its opening editorial).⁴⁶ Numerous groups and clinicians have voiced concerns about overdiagnosis,⁴⁷ disease mongering,⁴⁸ and the use of unnecessary or even harmful procedures.⁴⁹

These new concerns prompted medical and clinical societies worldwide to launch campaigns aimed at reducing medicine overuse, under the broad umbrella slogan “Less is more”. The most well-known of these campaigns is the Choosing Wisely initiative, launched in 2012 by the US National Physician Alliance, following a 2010 call by Dr Howard Brody.^{50, 51} This initiative has since prompted numerous medical specialties, including nursing and pharmacy, to produce their own “Top Five”

lists of things that patients and clinicians should question.

Of the nearly 100 lists found on ChoosingWisely.org, a third concern geriatric medicine, highlighting the need for particular caution in this population. The Choosing Wisely initiative found echoes internationally in more than 20 countries, including Switzerland, where the first

“Smarter Medicine” lists were published in 2014.⁵²

Deprescribing

Identifying overuse, or even mis-use, of medical resources is, however, not the same as ending it; there are indeed complex interplays between financial incentives, social pressure, and clinical habits among other things, creating barriers to reducing overuse.⁴⁴

In the domain of drug treatment, the concept of deprescribing has gained a lot of momentum in the past decade. The term was coined in 2003 by Michael Woodward,⁵³ but the idea behind it dates back centuries:

stopping unnecessary or harmful medication. The addition of deprescribing to this conversation is its systematic approach and patient centred-ness. Defined in 2015 by Page and colleagues as “the process of withdrawal of an inappropriate medication, supervised by a health care professional with the goal of managing polypharmacy and improving outcomes”,⁵⁴ deprescribing implies an active cooperation between the patient and the clinician, and a focus on clinically relevant outcomes.⁵⁵

Like the Choosing Wisely campaign, the concept of deprescribing has garnered international momentum, with deprescribing networks bringing together clinicians formed in multiple countries,^56-59 international symposia

taking place,⁶⁰ multiple entities producing clinical guidelines,^{61, 62} and, naturally, a growing body of research.

While some studies have been focused on other populations ^{63, 64} or on specific diseases,⁶⁵ research on deprescribing has mostly taken place in the elderly, as they are the main recipients of polypharmacy. Many studies have shown that, in this population, deprescribing would mostly be welcomed: a slim (50.8%)⁶⁶ to large (over 80%)^67-

70 majority of adults would agree to discontinue some medication. Deprescribing would be facilitated by many pervasive feelings towards illness and medication, such as dislike of taking them, the stigma associated with being

“sick”, or the fear of addiction.⁷¹ However, numerous barriers to deprescribing have been identified in patients:

fear of return of a condition or of symptoms, lack of motivation to initiate change, fear of missing out on potential benefits of drugs, etc.^71-73

Physicians were identified by patients and their relatives as a key influences in the deprescribing process, both for and against medication withdrawal.^72-74 They proved to be as conflicted as their patients regarding deprescribing:

while all studies reported that GPs agreed in principle with the idea of deprescribing,^75-77 they cited numerous barriers preventing them from doing so. Some of them were related to patients, who sometimes have no problem with polypharmacy and don’t see the point of deprescribing,⁷⁵ or are thought to be uncomfortable with discussing a balance between quality of life and life expectancy.⁷⁵ Other barriers stemmed from guidelines, who “do not cater for older patients”,⁷⁵ and organisation of healthcare, with some GPs expressing a reluctance to stop a treatment prescribed by someone else,^{76, 77} regretting a lack of time to engage in deprescribing,^{74, 77} and feeling generally not supported in this matter.⁷⁵

Few studies have investigated the point of view of other healthcare professionals; pharmacists mostly agreed with physicians about the need for deprescribing and the barriers to it in an Australian study, but had different opinions on which medicine to deprescribe.⁷⁸ Nurses agree as well that deprescribing is necessary, and note that the organisation of healthcare systems is major barrier to it: the multiplicity of providers is considered a significant enabler of polypharmacy.^{79, 80}

Despite all these barriers, several trials of deprescribing interventions have taken place in the last decade. Their methodology were varied: some targeted specific medication classes,^81-84 other polypharmacy as a whole;⁸⁵ some trialled medication review-like interventions,^{86, 87} and others educational approaches;^{82, 84} some interventions were performed by physicians,⁸⁸ others by pharmacists or interprofessional teams.^{85, 87} The goal of these trials were multiple: improving patient adherence,⁸⁹ reducing the use of PIMs or polypharmacy,^{86, 88} improving patient autonomy,^{90, 91} or limiting the risk of falls.⁹² This multiplicity of interventions and goals make assessing the overall impact of deprescribing challenging.

Page and colleagues, in a 2015 meta-analysis of more than 100 studies,⁹³ did not find deprescribing to reduce mortality overall, but found a significant reduction for patient-specific interventions (like medication reviews) targeting polypharmacy (odds ratio 0.62 [0.43-0.88]),

in opposition to educational interventions. Although results were not statistically significant, a stronger trend for benefit was found in patients aged 65 to 79 years than for those 80 years and over.

A subsequent meta-analysis by Kua and colleagues focused on studies conducted in NHs; it included 41 RCTs, regrouping over 18’000 participants.⁹⁴ In this population, deprescribing interventions significantly reduced mortality (OR 0.90 [0.82-0.99]) and the use of PIMs (OR 0.41 [0.19-0.89]), but not hospitalisations (OR 0.72 [0.31-1.66]) or falls (OR 0.85, [0.73-1.00]). Subgroup results confirmed the conclusion of Page and colleagues that patient-centred interventions were the most beneficial: the reduction in mortality found by Kua was strongly driven by the subgroup of studies that used medication reviews (OR 0.74 [0.65-0.84]), and these

interventions showed a reduction in the number of NH residents experiencing a fall (OR 0.76 [0.62-0.93]).

An area in which deprescribing has not shown beneficial effect is health-related quality of life (QoL): following a systematic review,⁹⁵ Pruskowski and colleagues concluded that deprescribing did not improve quality of life, although they noted that studies were extremely heterogeneous in terms of populations, QoL measurement, and medication targeted for deprescribing.

Many questions remain open concerning deprescribing:⁹⁶ what are its long-term effects? In what population, beside the elderly, could it be beneficial? What is the best way to implement it? Can it be transferred in routine practice while retaining its effectiveness? Fortunately, new evidence regarding its effects keep mounting: at the time of writing, 53 studies of deprescribing were listed as active on ClinicalTrials.gov.

Swiss context

Switzerland is a federal country; while styled the Swiss Confederation, it is technically a federation, with a constitution organisation the division of responsibilities between the federal government and the constituting cantons. The Swiss constitution places some responsibilities in the organisation of health care in the hands of the cantons, while others are regulated by federal law and administration. Cantons, for example, plan and administer public hospitals, jointly finance them with health insurers, and license and supervise healthcare professionals (physicians, pharmacists, nurses, etc.) practicing on their territories. Federal laws govern, among other things, the organisation of health insurance coverage, mandating that all residents must be covered for basic care, and the federal administration regulates drugs and medical devices on the market.⁹⁷

Cantonal prerogatives lead to some differences in the organisation of healthcare delivery in some sectors.

Physicians’ tariff points, for example, are set at the cantonal level, with differences of up to 18% between cantons. Another sector in which marked cantonal differences exist is long-term care, be it institutional care (e.g. NHs) or ambulatory care (home hospital).

Nursing homes in Switzerland

The provision of long-term care is supervised by cantons, with some of them devolving part of these responsibilities to local towns or cities.⁹⁷ Long-term care institutions tasked with caring for a geriatric population requiring medical care (NHs) account for the overwhelming majority of long-term care beds in Switzerland (excluding institutions for the mentally or physically handicapped):

their 95’259 beds represented 98% of the total in 2017.⁹⁸ This amounts to 61 beds for every 1’000 inhabitants 65 years and older, but this overall number masks strong differences between cantons, with Aargau having over 100 beds for 1’000 inhabitants over 65 in 2018, and Valais only 46.⁹⁹ Following population aging and an increasing use of

i Planification Informatisée des Soins Infirmiers Requis, the resident evaluation system used by some cantons’ NHs.

ii Ordonnance sur les prestations de l’assurance des soins, defining the amount paid by health insurers for care in nursing homes, depending on the number of daily minutes of nursing care required. OPAS classes are defined according to standardised evaluation tools, among them PLAISIR.

home-care services,⁹⁷ this number has mostly shrunk during the past years (it was 67 per 1’000 inhabitants over 65 in 2010 in Switzerland as a whole), although some cantons experienced strong growth (Aargau had 59 beds per 1’000 inhabitants over 65 in 2010), highlighting differences in cantonal policies.

The population of these NHs has also changed over the past 20 years: the increased use of home-care services mean that people are able to live at home longer; they then enter a NH, not at a later age (the average age of residents has not changed since 2010), but at a later point in life, with fewer autonomy and more dependency. For example, in the cantons using the PLAISIRⁱ resident evaluation system (Genève, Vaud, Neuchâtel, Jura), the proportion of residents with “very limited or null” orientation capabilities went from 48% in 2000 to 61% in 2018, denoting a rise in cognitive problems; for mobility, this proportion was 83% in 2000, and 91% in 2018.¹⁰⁰ Similarly, the proportion of residents requiring up to 100 minutes of nursing care per day (OPAS ⁱⁱ classes 1-5) shrunk between 2000 and 2018 in these cantons, from 34% to 17%, while the proportion of residents requiring more than 220 minutes per day (OPAS class 12) rose from 15% to 23%.¹⁰⁰ Residents also tend to enter a NH closer to death: in Switzerland as whole, the average length of stay in a NH went from 4.0 years in 2010 to 2.4 years in 2018.^{99, 101}

Physicians caring for NH residents in Switzerland are usually not employed by the NH, but general practitioners (GP) in a private practice, although some institutions affiliated with hospitals are served by hospital physicians.

Some large NHs are served by multiple physicians, and some residents choose to keep their community GP after their entry in the home; most cantons thus mandate that each NH has a responsible physician to coordinate the work of its peers. NH physicians are supported by a network of independent specialists (e.g. geriatricians) and nurses (e.g. wound care specialist nurse), support units

(e.g. palliative care units, psycho-geriatric units), and institutions (e.g. specialised hospital units for dementia patients).

Different models of drug provision in NHs

A significant aspect in which cantonal organisation for NHs differ is the provision of drugs. Two examples will be detailed and compared, as they are highly relevant to this thesis: the model for provision of drugs in the NHs of Vaud, with an outpatient model, and those of Fribourg, with a hospital-like model in force until 2018.

In the Canton de Vaud, a large, French-speaking canton, NH residents are not considered inpatients; they are instead classified as ambulatory patients, and the provision of drugs is similar to that of their home-dwelling peers.

Drugs are provided to the residents by a public pharmacy, or sometimes a hospital pharmacy, with each box belonging to the recipient; drugs are billed to the residents’ insurers as for regular community pharmacy customers. In this model, the NH does not stock drugs beside those currently in use by the residents. NH residents are notionally free to choose the pharmacy providing their drugs, but, in practice, very few of them exert this choice; instead, the NH usually choses a pharmacy providing the drugs for the whole institution.

This organisation has some advantages: NHs face no pressure to ration drugs, as they do not bear their cost, and residents are theoretically free to choose who provides their treatment. However, this model also presents significant disadvantages: neither NHs, physicians, nor pharmacies are incentivised to rationalise drug use, as none of them face economic pressure to do so; the drugs remain the property of the resident, which prevents their re-use in the institution upon discontinuation of treatment; and pharmacies fight sometimes bitterly to attract a NH’s custom, as it proves quite lucrative.

This model is the one found most commonly in Western Switzerland, with minor local variations; in the German- speaking part, the existence of dispensing physicians, who provide the drugs themselves, leads to a very similar organisation.

In contrast with the outpatient model found in Vaud was the inpatient model of Fribourg. Since 1991, NHs in the canton of Fribourg negotiated a flat fee for the provision of drugs to their residents with the health insurers. In this model, NHs were responsible for directly purchasing drugs used by their residents, and insurers payed a fixed fee for each day spent in the home by a policyholder.

A similar fee was negotiated for the provision of care products (e.g. wound care products, incontinence products). Purchase and distribution of the drugs were supervised by a pharmacist mandated by the NH, as part of an integrated pharmacy service (IPS) financed by a separate flat fee (see the following section for a complete description of the IPS). Drugs were purchased in bulk, often directly from the manufacturer at a negotiated price for all the NHs of the canton, and used in the NH as in hospitals, with no nominative boxes, except for some specific products (e.g. creams, multi-dose injections, ophthalmic products).

This model, very similar to the one found in hospitals with diagnosis related group (DRG) financing, had the potential to lead to severe rationing, as NHs bore a significant economic risk: a single resident requiring high- cost treatment could lead to severe financial difficulties for the institution. To prevent this, a risk-mutualisation scheme was put into practice: NHs could keep 70% of any benefit they had from the flat-fee, with the remaining 30%

feeding a “rainy-day fund”, from which NHs could draw in case of justified deficit.

This model, combined with the IPS, proved successful in containing drug costs; this was reflected in the reduction of the fee over time: starting at 9 Swiss francs (CHF) per resident and per day in 2002, the fee went down to 5.50 CHF in 2018. The model was however scrapped by the health insurers in mid-2018, following a change in federal law that required them to provide detailed drug invoice data to regulatory agencies; such data were indeed not directly available to them in this model. NHs in Fribourg have since reverted to the ambulatory model found elsewhere in Western Switzerland, with community pharmacies providing nominative drugs to their residents.

Integrated Pharmacy Service in NHs

Interprofessional collaborative practice has been a growing focus of healthcare systems evolution since the 1990s:¹⁰² the lack of collaboration between different professions has been recognised as contributing to sub- optimal patient care, and improving collaborative practice is expected to help mitigate the global health crisis brought by demographic change.^{103, 104}

In line with similar developments occurring in several European countries since the 1980s,¹⁰⁵ a novel model of collaborative practice started in the mid-1990s in the Canton of Fribourg, under the initiative of local practitioners: physicians-pharmacists quality circles aiming to improve drug prescribing. A key point differentiating these circles from other quality- improvement initiatives were their interprofessional nature: composed of up to 10 GPs, the meetings of these quality circles (QC) were moderated by a specially trained pharmacist. These QC met regularly to critically review new drugs on the market and new guidelines, benchmark their participants’ practice against each other and a control group using drug prescription data provided by the pharmacist, and create local treatment consensus prioritising effectiveness, safety and efficiency.¹⁰⁶ This model of collaboration proved successful in containing the rise in drug costs in the early 2000s, and improved generic drugs penetration and prescription quality indicators.¹⁰⁶ These physician-pharmacist QCs have since spread in the whole Western Switzerland, with over 100 circles active in 2019, and a similar collaboration being trialled with paediatricians.

This model of collaboration provided a framework for the creation of an IPS in the NHs of Fribourg when, in 1999 and 2000, changes in the cantonal legal framework mandated the presence of a pharmacist in NHs to supervise drug deliveries and required that this pharmacist provides pharmaceutical care services.^{107, 108}

Following developments made in some NHs of the canton, this IPS consisted of the following components:

· General services, covering the legal requirements, drug purchases and stock management, and super- vision of the drug supply in the NH;

· Rationalisation and safety of therapy, including pharmacoeconomic analysis of drug consumption in the NH, recommendations for improvement of drug therapy, and definition of local treatment consensus with the NH physician(s), akin to the activities taking place in QCs;

· Annual report on drug consumption in the NH, including monitoring of the application of the consensus and clinical recommendations.

This new model was formalised in a convention between the Fribourg NH association and the health insurers, and approved by the Fribourg government in 2002.

The pharmacist’s services were financed by a flat fee, separate from the one for drug provision, of 1 CHF per resident and per day. Pharmacists performing the IPS were supported by a coaching program that included training courses, individual feedback, and inter- professional symposia.¹⁰⁹

The IPS program was monitored by an independent academic team that provided annual benchmarking on drug consumption and feedback to NHs and stakeholders.

An analysis of data from 1998 to 2005 showed that the IPS had a significant impact on drug costs, with constant increase between 1998 and 2001, and constant decrease from the introduction of the service in 2002 to 2005.¹⁰⁹ This positive trend continued for much of the lifetime of the program, with cost reduction reaching 31.5% in 2015 compared to 2001.ⁱ The last years of the service (2016 to 2018) saw an increase in drug costs, but the cumulative savings between 2001 and 2018 were still 22.9%. A more detailed description of the program can be found in a paper by Bugnon and colleagues.¹¹⁰

This positive impact was widely publicised,¹¹¹ and generated political interest in the neighbouring canton of Vaud,¹¹² resulting in investigations into the launch of a similar IPS from 2008 to 2010,¹¹³ and a pilot phase starting in 2010 with 13 NHs. Following this pilot phase, recruitment of NHs to enter the program continued throughout 2011 to 2016, and virtually all NHs had joined the project at the start of 2017.

The two programs were very similar, with pharmacists tasked in both cantons with the critical appraisal of drugs used in the NH, organising regular meetings, called quality circles, with NH physicians and nurses in order to devise local treatment consensus, and producing an annual report on drug use in the NH. Two main differences between the programs stem from the differences in drug provision arrangements between the cantons: as drugs in Vaud are

i Source: Meier C. and colleagues, Résultats de l’assistance pharmaceutique dans les EMS fribourgeois: Étude comparative 2017- 2018 (1er semestre), unpublished report by the Commmunity pharmacy unit, Unisanté, 2019

ii Source : Assistance pharmaceutique en EMS: Rapport de synthèse 2014, unpublished report by pharmaValais, 2015

iii Data from the NHs of Fribourg were not included in this analysis, as health insurers did not have access to detailed drug consumption data at the time. This led to the discontinuation of the Fribourg model of drug financing in 2018, as a legal mandate to provide these data to the Federal Office of Statistics for risk-compensation calculation came into force.

iv Source : Mena S. and colleagues, Assistance pharmaceutique dans les établissements médico-sociaux du Canton de Vaud: Rapport d’activités 2018, unpublished report by the Commmunity pharmacy unit, Unisanté, 2019

provided directly to the resident by a community pharmacy and not covered by a flat fee to the NH, the pharmacist tasked with the IPS, most often working in the pharmacy providing the drugs, did not have to manage purchases and stocks for the NH. General services were thus limited to the legal requirements, such as regular inspections of the NH drug storage premises and control of scheduled substances. The second difference was the source of funding for the IPS: while in Fribourg, pharmacists’ services were paid for by a fee coming from insurers, no such arrangement could be reached in Vaud, and the pharmacists’ services were funded by the cantonal government. Funding came in the form of fee-for-service, with each activity assigned a maximum billable fee, and a yearly budget reaching 2 million CHF in 2019. The third main difference between the Vaud and Fribourg program was the disparity in the definition of NHs: only institutions caring for the elderly were classified as NHs in Fribourg, while some NHs in Vaud cared for adults suffering from severe psychiatric problems or other, very specific populations, such as terminally-ill HIV patients.

A third pharmaceutical care service was started in the NHs of the canton of Valais in the 2000s; it borrows elements of the Fribourg model, with a flat-fee compensating pharmacists, but retains outpatient drug provision, as in Vaud. A marked difference from the other IPS is that each resident keeps their GP and pharmacy at entry in the NH, leading to a multiplicity of providers.

NHs in this canton were thus served by, on average, over 4 pharmacists and 11 GPs in 2014, with some having over 20 of each.ⁱⁱ In each NH, a single pharmacist is tasked with the organisation of QC in the institution; the responsible physician for the home is tasked with ensuring that the other physicians enact the resulting treatment consensus.

Despite these organisational hurdles, this IPS has reported positive results on the cost of medications, with a 20%

reduction in cost per resident and per day between 2009 and 2014, although data were not analysed by an independent monitoring team, but rather by the professional association of pharmacists of this canton.

While no peer-reviewed results on the effects of the IPS in Vaud have been published, unpublished analysis confirmed its positive impact on drug costs. The first one, out carried by Mrs Annette Jamieson, from the Helsana health insurer, was performed on the data relative to the drug consumption of 92’027 policyholders residing in NHs between 2009 and 2014. It showed that the costs of drugs provided to these residents decreased in cantons where an IPS was active (Vaud and Valaisⁱⁱⁱ), whereas it increased where no IPS was present.¹¹⁴ These findings were confirmed by the multiple analysis performed by the monitoring team for this IPS and presented yearly to participants and stakeholders: in the most recent annual report,^iv cost savings were estimated at between -1.8% and

-5.7% per year since IPS start, depending in the mission of the NH.

It is not known, however, if these good financial results translate into better care for the residents. Indicators such as the hospitalisation rate or the death rate provide few meaningful information, as, as seen before, the population

of these NHs changed during the course of these IPSs.

Concerning the use of PIMs, the IPS seem to have few impacts: A. Jamieson compared the rate of prescription of PIMs in NHs with or without an IPS, and found no differences, with roughly 50% of NH residents having received at least one PIM in 2014.¹¹⁴

The OLD-NH project

This observation, and the renewed focus on quality of prescribing brought about by the deprescribing movement, led to the conceptualisation of the Opportunities and Limits to Deprescribing in Nursing Homes (OLD-NH) project in 2015: the close collaboration between physicians, nurses, and pharmacists fostered by the IPS provided a good opportunity to further develop interprofessional practice, in search of ever-better care of NH residents. Given the continued use of PIMs in NHs, and the high prevalence of polypharmacy, implementing deprescribing interventions was a logical next step.

In 2015, the Swiss National Science Foundation issued a call for proposals for the 74^th National Research Program (NRP), titled “Smarter Health Care”.¹¹⁵ Focused on

“provid[ing] insight into health care structure and utilization in Switzerland” and on improving the health outcomes for patients with multiple conditions, this NRP included three modules: “Countering under- and overuse to improve allocation of resources”, “Coordination and collaboration among health care professionals”, and

“Caring for patients with multiple chronic conditions”.

The situation of NH residents in Switzerland align perfectly with the goals of NRP 74: all of them are, quasi by definition, affected by multiple chronic conditions; the existence of mis- and over-use of drugs is a quasi-certainty, given what is known of NH residents elsewhere, and under-use may also be present; and solving these problems require intense interprofessional collaboration. The OLD- NH project was thus submitted, and accepted by, the NRP 74. The overarching goal of OLD-NH is to provide evidence regarding the effectiveness and implementation of deprescribing intervention in NHs where an interprofessional collaboration is already active.

Annexes 1 and 2 detail the submission to the NRP 74.

Structure of the OLD-NH project

Designed as a mixed-methods research project, OLD-NH consists of two phases, as shown on Figure 1. The first, exploratory, aims to describe the use of PIMs in NHs with an active ISP, and to understand residents’, their relatives’, and professionals’ points of view on PIMs and deprescribing. The first aim was realised through a pharmacoepidemiologic analysis of data collected for the monitoring of the IPS in Fribourg and Vaud; the second, through qualitative research involving NH residents, their relatives, and physicians, nurses and pharmacists active in an IPS. This first phase took place between 2016 and the end of 2017.

The second phase was interventional and started at the end of 2017. Its goal was to trial the effectiveness and implementation of two consecutive deprescribing interventions in the NHs of Vaud and Fribourg where an IPS is well established. The interventions tested built on the existing interprofessional collaborations fostered by the IPS, and followed its structure, and their design were informed by the results of the exploratory phase. The first one, called Quality Circle-Deprescribing Module (QC- DeMo), was a deprescribing-specific module to be enacted in the existing QCs in the NHs, resulting in a NH-level deprescribing consensus, focused on reducing the use of PIMs.

This first intervention was expected to have a broad impact on PIM use with a relatively minimal effort, and so to be highly cost-effective. However, it would not have been able to address all possible PIMs used by NH residents, as their clinical situation vary greatly. The second intervention, an Individual Deprescribing Intervention (IDeI), was therefore focused on the residents most heavily medicated, and thus most likely to receive PIMs. It took place one year after the QC-DeMo intervention, and was based on medication review methodology. Such complex interventions, requiring the

Figure 1: design overview of the OLD-NH project; QC-DeMo: Quality Circle-Deprescribing Module; IDeI: Individual Deprescribing Intervention.

2016 2017 2018 2019

IDeI study

Economic and implementation evaluation QC-DeMo study

Exploration phase Intervention phase

Qualitative studies Epidemiologic analysis