Gac Sanit. 2019;33(2):106–111 Original article Reduction of pharmaceutical expenditure by a drug appropriateness intervention in polymedicated elderly subjects in Catalonia (Spain) Lluís Campinsa , Mateu Serra-Pratb,c,∗ , Elisabet Palomerab , Ignasi Bolibard,e , Miquel Àngel Martínezf , Pedro Gallog a Pharmacy Department, Hospital de Mataró, Consorci Sanitari del Maresme, Mataró (Barcelona), Spain b Research Unit, Consorci Sanitari del Maresme, Mataró (Barcelona), Spain c CIBER de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain d Public Health and Clinical Epidemiology Department, Institut de Recerca Biomèdica Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain e CIBER de Epidemiología y Salud Pública (CIBERESP), Spain f Argentona Primary Care Centre, Consorci Sanitari del Maresme, Argentona (Barcelona), Spain g Department of Sociology, Faculty of Economics and Business, University of Barcelona, Barcelona, Spain a r t i c l e i n f o a b s t r a c t Article history: Objective: To assess the monetary savings resulting from a pharmacist intervention on the appropriate- Received 21 June 2017 ness of prescribed drugs in community-dwelling polymedicated (≥8 drugs) elderly people (≥70 years). Accepted 11 September 2017 Method: An evaluation of pharmaceutical expenditure reduction was performed within a randomised, Available online 20 November 2017 multicentre clinical trial. The study intervention consisted of a pharmacist evaluation of all drugs prescribed to each patient using the “Good Palliative-Geriatric Practice” algorithm and the “Screening Tool Keywords: of Older Persons Prescriptions/Screening Tool to Alert doctors to Right Treatment” criteria (STOPP/START). Aged The control group followed the routine standard of care. A time horizon of one year was considered and Pharmaceutical services Inappropriate prescribing cost elements included human resources and drug expenditure. Polypharmacy Results: 490 patients (245 in each group) were analysed. Both groups experienced a decrease in drug Primary health care expenditure 12 months after the study started, but this decrease was significantly higher in the inter- Drug costs vention group than in the control group (−14.3% vs. − 7.7%; p = 0.041). Total annual drug expenditure decreased 233.75 D /patient (95% confidence interval [95%CI]: 169.83-297.67) in the intervention group and 169.40 D /patient (95%CI: 103.37-235.43) in the control group over a one-year period, indicating that 64.30 D would be the drug expenditure savings per patient a year attributable to the study intervention. The estimated return per Euro invested in the programme would be 2.38 D per patient a year on average. Conclusions: The study intervention is a cost-effective alternative to standard care that could generate a positive return of investment. © 2017 SESPAS. Published by Elsevier España, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Reducción del gasto farmacéutico mediante una intervención de adecuación de medicamentos en ancianos polimedicados de Cataluña (España) r e s u m e n Palabras clave: Objetivo: Evaluar los ahorros monetarios resultantes de la intervención de un farmacéutico orientada a Ancianos mejorar la adecuación de los fármacos prescritos en ancianos (≥70 años) polimedicados (≥8 medicamen- Servicios farmacéuticos tos) de la comunidad. Prescripción inadecuada Método: Se evaluó la reducción del gasto farmacéutico en el marco de un ensayo clínico aleatorizado y Polifarmacia multicéntrico. La intervención del estudio consistió en una evaluación de todos los fármacos prescritos Atención primaria de salud Costes de medicamentos a cada paciente utilizando el algoritmo Good Palliative-Geriatric Practice y los criterios Screening Tool of Older Persons Prescriptions/Screening Tool to Alert doctors to Right Treatment (STOPP/START). El grupo control siguió la práctica clínica habitual. Se consideró un horizonte temporal de un año y los elementos de costes incluyeron los recursos humanos y el gasto en medicamentos. Resultados: Se analizaron 490 pacientes (245 por grupo). La disminución del gasto farmacéutico a los 12 meses fue significativamente mayor en el grupo de intervención que en el grupo control (−14,3% vs. − 7,7%; p = 0,041). El gasto anual en medicamentos disminuyó 233,75 D por paciente (intervalo de confianza del 95% [IC95%]: 169,83-297,67) en el grupo de intervención y 169,40 D por paciente (IC95%: 103,37-235,43) en el grupo control, indicando un ahorro farmacéutico de 64,30 D por paciente/año atribuible a la intervención del estudio. Se ha estimado un retorno de 2,38 D por cada euro invertido en el programa. ∗ Corresponding author. E-mail address: mserra@csdm.cat (M. Serra-Prat). https://doi.org/10.1016/j.gaceta.2017.09.002 0213-9111/© 2017 SESPAS. Published by Elsevier España, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc- nd/4.0/). L. Campins et al. / Gac Sanit. 2019;33(2):106–111 107 Conclusiones: La intervención en estudio es una alternativa rentable a la atención estándar, que podría generar un retorno positivo de la inversión. © 2017 SESPAS. Publicado por Elsevier España, S.L.U. Este es un artı́culo Open Access bajo la licencia CC BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/4.0/). Introduction discussed recommendations for each drug with the patient’s physician on a face-to-face visit in order to come up with a final set Population ageing has led to an increase in the prevalence of recommendations (stop, start or change medication or dosage). of chronic diseases and in the use of health resources including Finally, these recommendations were discussed with the patient, medication. People over 65 years, which have a high prevalence and a final decision was agreed by physicians and their patients in of chronic diseases and are often treated with multiple drugs,1 a face-to-face routine visit. A safety control visit was planned one represent 17% of the current Spanish population and are respon- month later. All changes in prescribed medication were registered sible of 70% of pharmaceutical expenditure.2 Moreover, in the last in the electronic clinical notes and in the study’s record form. years, pharmaceutical expenditure has growth much more than the The control group received usual clinical practice. Overall, 503 gross domestic product in most European countries, threatening patients were recruited; 251 in the control group and 252 in the the sustainability of public health care systems.3 On the other hand, intervention group, in which 2709 drugs were evaluated. The study potentially inappropriate prescribing (PIP) comprises a number protocol was approved by the local ethical committee (CEIC 05/12) of suboptimal prescribing practices, including inappropriate dose and all participants gave their consent by writing before inclusion. or duration of medication, drug-drug interactions, drug-disease interactions, and use of medications that have a significant risk Cost elements considered of an adverse drug event.4,5 PIP has been found to be frequent in elderly population and associated with morbidity, adverse drug We aimed to assess the reduction in pharmaceutical expendi- events, hospitalizations, and health care expenditures.6,7 For this ture alongside the clinical trial due to the pharmacist intervention reason, strategies aimed to improve the quality and safety of pre- in primary care in relation to the routine clinical practice (stan- scription in the elderly population can generate substantial health dard of care by the general practitioner), following the ISPOR Good and economic benefits.8,9 Several criteria and algorithms have Research Practices report for reporting economic evaluation along- been developed to reduce PIP. One of the most used criteria is side clinical trials.18 We have considered a time horizon of one year the Screening Tool of Older Persons Prescriptions/Screening Tool following intervention. to Alert doctors to Right Treatment (STOPP/START).10 Likewise, Cost elements considered in the study included particularly an algorithm used to enable more rational and appropriate use the use human resources and consumption of drugs. In relation of medication in elderly people is the Good Palliative-Geriatric to human resources, it was estimated that the study interven- Practice (GP-GP).11 Some authors have assessed the safety and tion required a mean of 30 minutes of a pharmacist per patient effectiveness of interventions using these tools. Improvements in (drug evaluation and discussion with physician) and 20 minutes drug appropriateness and reduction in number of medications of a physician per patient (discussion with pharmacist and an have been reported.12,13 Additionally, strategies including a clini- additional visit with the patient). Monetary valuation of time was cal pharmacist can help decrease PIP and optimize patient therapy, possible using salary data available through the 2012 collective resulting in better clinical outcomes.14 However, limited evidence labor agreement (Catalan Health Service). The cost per hour, for exists about economic evaluations of these interventions.15,16 The both physicians and pharmacists, was 32.44 D /hour which included objective of the present study was to assess the economic impact social security contributions but not structural costs. Drug prices, in drug expenditure of a pharmacist intervention on prescriptions number of dispensed prescriptions, number of “generic drugs” and to community-dwelling polymedicated elderly people. number of “new drugs” were obtained from the administrative pharmacy database of the Catalan Health Service. “New drugs” Method are considered drugs commercialized over the last five years and qualified with category C (most suitable therapeutic alternatives Clinical trial design exist) or D (alternative therapeutic comparative information is not conclusive) by the Catalan Health Service. Only dispensed medica- A randomized, open-label, multicenter, parallel-arm clinical tion costs were considered, so real cost in drug expenditure was trial was conducted in seven primary care centers in the city of contemplated. The return of investment of the study intervention Mataró and Argentona (Barcelona, Spain) (122,905 and 11,718 has been calculated dividing the savings in drug expenditure by the inhabitants respectively, with 13,290 and 1,194 aged 70 years and cost of the intervention. over, respectively) to assess the effect of a pharmacist interven- tion on the appropriateness of prescribed drugs. Details of this Data analysis study were published elsewhere.17 In brief, the study population included a randomly selected sample of community-dwelling (non- A sensitivity analysis was performed based on three theoretical institutionalized) elderly people aged 70 years and older, receiving scenarios, the first being the basal scenario (30 minutes pharmacist eight or more drugs. Recruitment took place from February and and 20 minutes physician time), the second being a rather more May 2012 and participants were pre-selected from the primary care optimistic one (20 minutes pharmacist and 15 minutes physician), database and randomized with allocated concealment to one of the and a third one labeled as conservative scenario (40 minutes phar- two study arms. The intervention, which took place no more than macist and 30 minutes physician per patient). Among recruited a month after the recruitment visit, included a trained and expe- patients, 13 (2.58%) died during the 12 months follow-up (six rienced clinical pharmacist evaluating all drugs prescribed to each in the control group and seven in the intervention group), and patient using the GP-GP algorithm and basing their decision about were excluded from the cost analysis. The number of dispensed appropriateness on the STOPP/START criteria. The pharmacist drugs in the 12 months before the intervention was also obtained 108 L. Campins et al. / Gac Sanit. 2019;33(2):106–111 using the same data sources. The difference between study groups in drug consumption 12 months before and 12 months after the intervention was also computed. Continuous variables (total drug expenditure 12 months after intervention, incremental drug expenditure 12 months before versus after intervention, total number of recipes 12 months after intervention and incremental number of recipes 12 months before versus after intervention) were described using means or medians (in case of non-normal distri- bution) and standard deviations. Basal and follow up comparisons between groups were tested by the t-test (for variables with nor- mal distribution) or the Mann Whitney U test (for variables without normal distribution). Statistical significance was established at a p value < 0.05. To estimate the sample size, the main outcome variable was the pharmaceutical expenditure 1 year before and 1 year after the study intervention (paired data). For an alpha risk of 0.05 and a beta risk of 0.2 (two-tailed tests), it was estimated that 81 subjects were required to detect a difference equal to or greater than 250 D in pharmaceutical expenditure, assuming a standard deviation (SD) of 800 D . Results Figure 1. Evolution of median of drug expenditure (D ) per patient 12 months before and 12 months after the intervention. After excluding patients who died (n = 13), 245 patients were recruited to control group (78.7 years, SD: 5.5; 57.9% women) and 245 to intervention group (79.1 years, SD: 5.4; 61.6% women). No prescriptions, and a significant increase in both groups in the per- statistically significant differences were observed between the two centage of generic drugs prescribed. We also observed a significant groups in the number of drug prescriptions and drug expenditure increase in the number of new drug prescribed in the control during the 12 months before pharmacist intervention, indicating group. Total annual drug expenditure in the intervention group that both groups were originally comparable. We observed, how- decreased from 317,520.00 D (pre-intervention) to 260,263.00 D ever, statistically significant differences in drug expenditure and (post-intervention), representing 233.75 D (95% confidence inter- in the number of prescriptions during the 12 months after inter- val [95%CI]: 169.83-297.67) saved per patient (1,296.00 D /patient vention. As shown in Table 1, although both groups experienced a pre vs. 1,062.30 D /patient post). Similarly, total annual drug expen- decrease in drug expenditure 12 months after the study started, diture in the control group decreased from 338,271.00 D to this decrease was significantly higher in the intervention group 296,768.00 D , which results in 169.40 D (95%CI: 103.37-235.43) than in the control group. Similarly, the rise in generic drug saved per patient over one-year period (1,380.70 D /patient pre vs. prescriptions was significantly greater in the intervention group. 1,211.30 D /patient post). The resulting incremental drug expendi- Table 1 also reports on total cost and total number of prescriptions ture of standard care over pharmacist intervention is 64.30 D per before and after the pharmacist intervention. It shows a signifi- patient each year. In other words, 64.30 D would be the cost savings cant reduction for both groups in total costs, in the total number of per patient a year attributable to the study intervention. Table 1 Prescription patterns and associated annual costs/expenditures per patient before and after the pharmacist intervention. Intervention group Control group p N = 245 N = 245 Mean (SD) 95%CI Mean (SD) 95%CI 12 months before intervention Annual drug expenditure/patient (D ) 1,296.00 (1,190.94-1401.06) 1,380.70 (1,271.21-1490.19) 0.275a (839.00) (874.40) Annual number of prescriptions/patient 127.9 (43.6) (122.4-133.4) 134.3 (50.4) (128.0-140.6) 0.228a Prescriptions in generic drugs (%) 39.1 (15.8) (37.1-41.1) 40.6 (16.4) (38.5-42.65) 0.299b Prescriptions in new drugs (%) 0.9 (2.7) (0.6-1.2) 0.7 (2.3) (0.4-1.0) 0.972a 12 months after intervention Annual drug expenditure/patient (D ) 1,062.30 (961.79-1,162.81) 1,211.30 (1,108.07-1,314.53) 0.010a (802.70) (824.40) Annual number of prescriptions/patient 109.1 (40.6) (104.0-114.2) 118.5 (43.1) (113.1-123.9) 0.013b Prescriptions in generic drugs (%) 46.3 (17.1) (44.2-48.4) 45.5 (17.2) (43.3-47.6) 0.585a Prescriptions in new drugs (%) 1.1 (3.2) (0.7-1.5) 1.4 (3.0) (1.0-1.8) 0.064a Before-after differences Reduction in drug expenditure (D ) 233.75 (510.46) (169.83-297.67) 169.40 (527.35) (103.37-235.43) 0.171a Reduction in drug expenditure (%) 14.3 (40.8) (19.4-9.2) 7.7 (42.7) (13.0-2.35) 0.041a Reduction in number of prescriptions (%) 12.5 (22.0) (15,2-9,75) 8.9 (23.4) (11.8-2.3) 0.091b Increase in generic drug prescriptions (%) 7.4 (11.7) (5.9-8.8) 5.1 (10.6) (3.8-6.4) 0.025b Increase in new drug prescriptions (%) 0.2 (3.0) (−0.2-0.5) 0.7 (2.4) (0.4-1.0) 0.007a 95%CI: 95% confidence interval; SD: standard deviation. a Mann Whitney U test. b t-test. L. Campins et al. / Gac Sanit. 2019;33(2):106–111 109 Figure 4. Evolution of percentage of new drugs per patient 12 months before and Figure 2. Evolution of median of prescriptions per patient 12 months before and 12 months after the intervention. 12 months after the intervention. the program we would be saving an average of 2.38 D per patient a year (ranging from 1.70 D to 3.40 D ). Discussion Our study reveals that a one-time pharmacist intervention in primary care allows for a 12 months accumulated reduction in total drug prescription and expenditure in community-dwelling poly- medicated elderly people. It also shows an increase in the number of prescribed generic drug and a reduction in the number of pres- cribed “new drugs”. Since savings in drug expenditure are greater than costs derived from the intervention, the pharmacist interven- tion can be a cost-effective alternative to standard of care rendering a positive return on investment (2.38 D ) per euro. Our results are consistent with other findings from previous studies evaluating the economic impact of pharmacist inter- ventions. In a series of systematic reviews conducted for the American College of Clinical Pharmacy, the economic value of clinical pharmacist services was summarized and evaluated. The first review, conducted by Schumock et al.,19 evaluated articles Figure 3. Evolution of percentage of generic drugs per patient 12 months before published from 1996-2000. They concluded that for every $1 and 12 months after the intervention. invested in clinical pharmacy services, $4 was achieved in reduced costs or other economic benefits. A review by Pérez et al.,20 that included articles published between 2001-2005, showed sim- Figures 1 and 2 displays the monthly evolution of median ilar results. The most recent published review on the topic21 drug expenditure and median number of prescriptions during 12 incorporated fewer number of studies, published between 2006- months pre-intervention and 12 months post-intervention for both 2010, and could not provide a benefit/cost ratio as previous groups. Further, the higher percentage of generic drugs prescribed reviews did. One important difference between our study and in the intervention group remained largely unchanged throughout other published studies included in these reviews is that the latter the one-year follow-up (Fig. 3). Finally, as regard the prescription of focused more on specific clinical conditions. Brennan et al. demon- new drugs (Fig. 4), it is the standard care group that shows a rather strated a return on investment ratio of 3:1 using an integrated more ascendant pattern, particularly over the last 4 months in the pharmacy program to improve medication prescription and adher- study. ence rates in diabetes patients.22 Pharmaceutical interventions Table 2 presents the additional costs and savings under three have also proven to be cost-effective in pathologies such HIV,23 scenarios. The average annual saving resulting from the study inter- depression24 or hypertension.25 Despite these pieces of evidence, vention is 37.57 D per patient a year. According to the sensitivity there are very few studies that focused on the economic evalua- analysis performed, annual savings per patient range from 45.68 tion of a pharmacist intervention that aim at reducing potentially D (optimistic scenario) to 26.75 D per patient (conservative sce- inappropriate prescriptions and at improving drug appropriate- nario). If we were to estimate the return on investment of the study ness in community-dwelling polymedicated elderly people. When intervention, dividing cost savings (64.30 D ) by annual cost of inter- published, such studies showed very modest savings regarding vention for each scenario, we would argue that for 1 D invested in medication costs with no statistical significance.26 110 L. Campins et al. / Gac Sanit. 2019;33(2):106–111 Table 2 Sensitivity analysis of the annual benefits per patient considering three cost scenarios. Scenario Scenario 0, basal Scenario 1, optimistic Scenario 2, conservative (30 min pharmacist+ 20 min (20 min pharmacist+ 15 min (40 min pharmacist+ 30 min physician) physician) physician) Intervention Control Intervention Control Intervention Control Annual additional cost of intervention per 27.03 D 0D 18.92 D 0D 37.85 D 0D patienta Difference in benefit per patient between − 37.57 D − 45.68 D − 26.75 D groups (net savings) Return of investmentb 2.38 D 3.40 D 1.70D a Additional cost of intervention per patient results from adding the respective minutes of pharmacist and primary care physician at a cost of 32,44 D per hour. b Average savings for every euro invested in the program (obtained dividing cost savings (64,30 D ) by annual cost of intervention for each scenario). Monthly evolution of median cost, median prescriptions per the generalization of the economic impact of the intervention in patient and percentage of generic drugs showed a somewhat real-world practice. To overcome this limitation, we have selected parallel evolution on control and intervention groups indicating a comparator that represents the most realistic choice in real prac- that the initial gap between both groups generated by the pharma- tice. Other study limitations include: a) the intervention-to-control cist intervention had a long-lasting effect on both variables. This contagion, which may dilute the effect of the intervention; b) the effect appears to be slightly diluted one year after the intervention, exclusion of deaths from the analysis, which may carry an under- and perhaps indicates that another pharmaceutical intervention estimation of total drug expenditure but do not alter inter-group should be done as reinforcement. On the other hand, “new drugs” comparisons because of the balanced number of deaths between showed an increase in prescription over the last 4 months in the groups; and c) cost elements considered are only cost in drug study, pointing to a greater penetration of new products as thera- consumption and direct costs in human resources (time invested peutic options in this group. was a theoretical estimation), therefore more economic impact Although a significant reduction in drug prescription and expen- studies and full economic evaluations are required. ditures was observed resulting from the intervention, it is of In summary, the present study shows that the intervention of relevance to report that the control group also experienced a signifi- a clinical pharmacist in the primary care setting evaluating all cant reduction in drug expenditure itself during the follow-up study medication in polymedicated community-dwelling elderly sub- period. This fact can be partially attributed to the study design, jects is responsible for a reduction of approximately 7% in drug which was an open-label randomized clinical trial with possible expenditure. Such a community intervention may be a cost saving intervention-to-control contagion. The prescribing physicians who alternative with a possible positive return on investment. received recommendations from the pharmacist regarding patients in the intervention group also visited patients in the control group. Consequently, the control group have indirectly benefited from the intervention, possibly diluting the true effect of the intervention. Moreover, the decrease in drug prescription in the control group What is known about the topic? may also be explained by other measures put forward by the Cata- Potentially inappropriate prescribing has been found to lan Health Service to control drug expenditure in the primary care be frequent in elderly population and associated with mor- setting and by other important state control measures such as the bidity, adverse drug events, hospitalizations, and health care Royal Decree-Law 16/2012, which introduced the co-payment sys- expenditures. Several criteria and algorithms have been devel- tem for outpatient pharmaceutical services and the exclusion of oped to reduce it. However, limited evidence exists about more than 400 products from public funding. economic evaluations of these interventions. The reduction in total drug expenditure is largely a conse- quence of a decrease in the number of drugs prescribed (drug What does this study add to the literature? discontinuations), which accounts for 9.2% of total initial prescrip- tions. In addition, dose adjustments accounted for 6.9% and drug The intervention of a clinical pharmacist in the primary care substitutions for 3.1% of initial prescriptions17 . The use of generic setting evaluating all medication in polymedicated elderly sub- jects is responsible for a reduction of approximately 7% in total drugs had a limited impact in drug cost savings since the Spanish drug expenditure (a mean reduction of 64 D per patient a year). drug regulation does not allow for differences in publicly financed Such a community intervention is a cost saving alternative with prices between generic and non-generic drugs. Finally, it should be a positive return on investment. noted that although the prescription of new drugs is only a small percentage of overall drug prescription, the control group shows a more than three-fold increase in this respect when compared to the intervention group. Given the very high price of these new drugs, small differences in prescription frequency may have a relevant Editor in charge economic impact. Probably, the main strength of the study is its controlled and Miguel Ángel Negrín Hernández. randomized experimental design. There are a number of advan- tages of performing economic studies as part of an on-going clinical Transparency declaration trial.27 Among other benefits, it is argued that since economic evaluation largely depends upon the quality of the data generated, The corresponding author on behalf of the other authors gua- clinical trials are an efficient setting for economic analyses. Both rantee the accuracy, transparency and honesty of the data and the quality of the data and the greater control over potential information contained in the study, that no relevant information sources of bias favor clinical trials. However, the literature also has been omitted and that all discrepancies between authors have outlines some limitations, the most relevant to our study being been adequately resolved and described. L. Campins et al. / Gac Sanit. 2019;33(2):106–111 111 Authorship contributions 2. Blasco Patiño F, Martínez López de Letona J, Villares P, et al. El paciente anciano polimedicado: efectos sobre su salud y sobre el sistema sanitario. Inf Ter del Sist Nac Salud. 2005;29:152–62. L. Campins designed the study, contributed in the fieldwork and 3. Panteli D, Arickx F, Cleemput I, et al. Pharmaceutical regulation in 15 European wrote the manuscript. M. Serra-Prat designed the study, performed countries review. Health Syst Transit. 2016;18:1–122. the statistical analysis and wrote the manuscript. E. Palomera per- 4. Gallagher P, Barry P, O’Mahony D. Inappropriate prescribing in the elderly. J Clin Pharm Ther. 2007;32:113–21. formed the statistical analysis and review the manuscript. I. Bolibar 5. Spinewine A, Schmader KE, Barber N, et al. Appropriate prescribing in elderly review the manuscript with important contribution in metho- people: how well can it be measured and optimised? Lancet. 2007;370:173–84. dological aspects. M.A. Martínez, medical coordinator of the study, 6. Rivas-Cobas PC, Ramírez-Duque N, Gómez Hernández M, et al. Characteristics of potentially inappropriate prescribing of drugs in elderly polypathological contributed in the fieldwork and review the manuscript. P. Gallo patients. Gac Sanit. 2017;31:327–31. review the manuscript with important contribution in economic 7. Ryan C, O’Mahony D, Kennedy J, et al. Potentially inappropriate prescribing aspects. in an Irish elderly population in primary care. Br J Clin Pharmacol. 2009;68: 936–47. 8. Nicieza-García ML, Salgueiro-Vázquez ME, Jimeno-Demuth FJ, et al. Optimiza- Acknowledgments tion of information on the medication of polypharmacy patients in primary care. Gac Sanit. 2016;30:69–72. 9. Cahir C, Bennett K, Teljeur C, et al. Potentially inappropriate prescribing and The authors thank the study participants and ICS (Institut adverse health outcomes in community dwelling older patients. Br J Clin Phar- Català de la Salut) and CSdM primary healthcare professionals macol. 2014;77:201–10. who assisted with the study. REMEI Group members who par- 10. O’Mahony D, O’Sullivan D, Byrne S, et al. STOPP/START criteria for poten- ticipated in the fieldwork: Clara Agustí, Miren Maite Aizpurua, tially inappropriate prescribing in older people: Version 2. Age Ageing. 2015;44:213–8. Maria Alegre, Antònia Armada, Azhara Sánchez, Mireia Bancells, 11. Garfinkel D, Mangin D. Feasibility study of a systematic approach for discontin- Eugènia Barbena, Maria Bartolomé, Montserrat Bosch, Isaac Bux- uation of multiple medications in older adults: addressing polypharmacy. Arch adé, Mateu Cabré, Marta Calvo, Lluís Campins, Marcel·la Camps, Intern Med. 2010;170:1648–54. 12. Frankenthal D, Lerman Y, Kalendaryev E, et al. Intervention with the screen- Dolors Casabella, Toni Casanova, Gemma Casas, Rosa Castellanos, ing tool of older persons potentially inappropriate prescriptions/screening Salvador Castro, Berta Chaves, Sílvia Cid, Rosa Ma Coma, Enric tool to alert doctors to right treatment criteria in elderly residents of a Corona, Joan Domenech, Imma Esteva, Esther Fabré, Xavier Fab- chronic geriatric facility: a randomized clinical trial. J Am Geriatr Soc. 2014;62: 1658–65. regas, Pere Flores, Isabel Font, Consol Garcia, Vanesa Garcia, 13. Patterson SM, Cadogan CA, Kerse N, et al. Interventions to improve the appro- Teté González, Inés Gozalo, Teresa Gros, Teresa Gurrera, Grego- priate use of polypharmacy for older people. Cochrane Database Syst Rev. rio Hinojosa, Núria Jerez, Mercè Jiménez, Tamara Jiménez, Josep 2014:CD008165. 14. Kaboli PJ, Hoth AB, McClimon BJ, et al. Clinical pharmacists and inpatient medical Juanola, Lucia Jurado, Esther Limón, Pere Lledonet, Jordi Lloret, care: a systematic review. Arch Intern Med. 2006;166:955–64. Montse Lloret, Ainhoa López, David López, Carolina Luna, Mozgham 15. Gallagher J, McCarthy S, Byrne S. Economic evaluations of clinical pharmacist Mahramci, Vanessa Marta, Juan José Martí, Oriol Martí, Dolors interventions on hospital inpatients: a systematic review of recent literature. Int J Clin Pharm. 2014;36:1101–14. Martínez, Miquel Àngel Martínez, Mireia Massot, Laura Mateu, 16. Thomas R, Huntley AL, Mann M, et al. Pharmacist-led interventions to reduce Núria Mengual, Nacho Menjón, Mar Mir, Juan Carlos Montero, Pilar unplanned admissions for older people: a systematic review and meta-analysis Montero, Susana Morales, Josep Nuñez, Ana Palacio, Elisabet Palom- of randomised controlled trials. Age Ageing. 2014;43:174–87. era, Mercè Palomera, Mònica Papiol, Joan Pascual, Lourdes Pató, 17. Campins L, Serra-Prat M, Gózalo I, et al. Randomized controlled trial of an intervention to improve drug appropriateness in community-dwelling poly- Miquel Robusté, Ingrid Roca, Ana Roces, Mel Roger, Jordi Salabar- medicated elderly people. Fam Pract. 2017;34:36–42. nada, Fernando Samaniego, Dolors Sánchez, Elisa Sanz, Miriam 18. Ramsey SD, Willke RJ, Glick H, et al. Cost-effectiveness analysis alongside clin- Serra, Pere Serra, Mateu Serra-Prat, Cristina Serrano, Dorte Skiffter, ical trials II-An ISPOR Good Research Practices Task Force report. Value Health. 2015;18:161–72. Clara Soler, Pelin Son, Josep Sorribes, Pere Toran, Eulàlia Torrellas, 19. Schumock GT, Butler MG, Meek PD, et al. Evidence of the economic ben- Carles Tria, Yolanda Verde and Isabel Villarroya. efit of clinical pharmacy services: 1996-2000. Pharmacotherapy. 2003;23: 113–32. 20. Pérez A, Doloresco F, Hoffman JM, et al. ACCP: economic evaluations of clinical Funding pharmacy services: 2001-2005. Pharmacotherapy. 2009;29:128. 21. Touchette DR, Doloresco F, Suda KJ, et al. Economic evaluations of clinical phar- This project was funded by a grant from the Spanish Ministry of macy services: 2006-2010. Pharmacotherapy. 2014;34:771–93. 22. Brennan AT, Dollear JT, Hu M, et al. An integrated pharmacy-based program Health (Independent Health Research Ref. EC11-313) and a grant improved medication prescription and adherence rates in diabetes patients. from the Catalan Government Health Service (SLT/682/2012). These Health Aff. 2012;31:120–9. governmental funding bodies played no role in study design, data 23. Carnevale RC, Molino CGRC, Visacri MB, et al. Cost analysis of pharmaceutical care provided to HIV-infected patients: an ambispective controlled study. Daru. collection, analysis and interpretation or in the decision to approve 2015;23:13–5. publication of the finished manuscript. 24. Rubio-Valera M, Bosmans J, Fernández A, et al. Cost-effectiveness of a com- munity pharmacist intervention in patients with depression: a randomized controlled trial (PRODEFAR Study). PLoS One. 2013;8, 8e70588. Conflicts of interests 25. Polgreen LA, Han J, Carter BL, et al. Cost-effectiveness of a physician-pharmacist collaboration intervention to improve blood pressure control. Hypertension. None. 2015;66:1145–51. 26. Clyne B, Fitzgerald C, Quinlan A, et al. Interventions to address potentially inappropriate prescribing in community-dwelling older adults: a system- References atic review of randomized controlled trials. J Am Geriatr Soc. 2016;64: 1210–22. 1. Sanfélix-Gimeno G, Peiró S, Meneu R. Pharmaceutical prescription in primary 27. Shaya FT, Samant N. Cost studies in clinical trials. Expert Rev Pharmacoecon care. SESPAS report 2012. Gac Sanit. 2012;26 Supl 1:41–5. Outcomes Res. 2004;4:591–4.