title: Polypharmacy in chronic diseases-Reduction of Inappropriate Medication and Adverse drug events in older populations by electronic Decision Support (PRIMA-eDS): study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Multimorbidity is increasing in aging populations with a corresponding increase in polypharmacy as well as inappropriate prescribing. Depending on definitions, 25-50 % of patients aged 75 years or older are exposed to at least five drugs. Evidence is increasing that polypharmacy, even when guidelines advise the prescribing of each drug individually, can potentially cause more harm than benefit to older patients, due to factors such as drug-drug and drug-disease interactions. Several approaches reducing polypharmacy and inappropriate prescribing have been proposed, but evidence showing a benefit of these measures regarding clinically relevant endpoints is scarce. There is an urgent need to implement more effective strategies. We therefore set out to develop an evidence-based electronic decision support (eDS) tool to aid physicians in reducing inappropriate prescribing and test its effectiveness in a large-scale cluster-randomized controlled trial.
  
  
  METHODS
  The "Polypharmacy in chronic diseases-Reduction of Inappropriate Medication and Adverse drug events in older populations" (PRIMA)-eDS tool is a tool comprising an indication check and recommendations for the reduction of polypharmacy and inappropriate prescribing based on systematic reviews and guidelines, the European list of inappropriate medications for older people, the SFINX-database of interactions, the PHARAO-database on adverse effects, and the RENBASE-database on renal dosing. The tool will be evaluated in a cluster-randomized controlled trial involving 325 general practitioners (GPs) and around 3500 patients across five study centres in the United Kingdom, Germany, Austria and Italy. GP practices will be asked to recruit 11 patients aged 75 years or older who are taking at least eight medications and will be cluster-randomized after completion of patient recruitment. Intervention GPs will have access to the PRIMA-eDS tool, while control GPs will treat their patients according to current guidelines (usual care) without access to the PRIMA-eDS tool. After an observation time of 2 years, intervention and control groups will be compared regarding the primary composite endpoint of first non-elective hospitalization or death.
  
  
  CONCLUSIONS
  The principal hypothesis is that reduction of polypharmacy and inappropriate prescribing can improve the clinical composite outcome of hospitalization or death. A positive result of the trial will contribute substantially to the improvement of care in multimorbidity. The trial is necessary to investigate not only whether the reduction of polypharmacy improves outcome, but also whether GPs and patients are willing to follow the recommendations of the PRIMA-eDS tool.
  
  
  BACKGROUND
  This trial has been registered with Current Controlled Trials Ltd. on 31 July 2014 (ISRCTN10137559).
authors.affiliation: Institute of General Practice and Family Medicine, Witten/Herdecke University, Alfred-Herrhausen-Str. 50, 58448, Witten, Germany. Andreas.Soennichsen@uni-wh.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Sönnichsen
authors.affiliation: Institute of General Practice and Family Medicine, Witten/Herdecke University, Alfred-Herrhausen-Str. 50, 58448, Witten, Germany.
authors.forename: Ulrike S
authors.initials: US
authors.lastname: Trampisch
authors.affiliation: Institute of General Practice and Family Medicine, Witten/Herdecke University, Alfred-Herrhausen-Str. 50, 58448, Witten, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Rieckert
authors.affiliation: South Tyrolian Academy of General Practice, Bolzano, Italy.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Piccoliori
authors.affiliation: South Tyrolian Academy of General Practice, Bolzano, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Vögele
authors.affiliation: Institute of General Practice, Family Medicine and Preventive Medicine, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Maria
authors.initials: M
authors.lastname: Flamm
authors.affiliation: Institute of General Practice, Family Medicine and Preventive Medicine, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Tim
authors.initials: T
authors.lastname: Johansson
authors.affiliation: Centre of Primary Care, University of Manchester, Manchester, UK.
authors.forename: Aneez
authors.initials: A
authors.lastname: Esmail
authors.affiliation: Centre of Primary Care, University of Manchester, Manchester, UK.
authors.forename: David
authors.initials: D
authors.lastname: Reeves
authors.affiliation: Institute of General Practice, Rostock University Medical Centre, Rostock, Germany.
authors.forename: Christin
authors.initials: C
authors.lastname: Löffler
authors.affiliation: Institute of General Practice, Rostock University Medical Centre, Rostock, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Höck
authors.affiliation: Department of Medical Informatics, Biometry and Epidemiology, Ruhr University, Bochum, Germany.
authors.forename: Renate
authors.initials: R
authors.lastname: Klaassen-Mielke
authors.affiliation: Department of Medical Informatics, Biometry and Epidemiology, Ruhr University, Bochum, Germany.
authors.forename: Hans Joachim
authors.initials: HJ
authors.lastname: Trampisch
authors.affiliation: Duodecim Medical Publications, Helsinki, Finland.
authors.forename: Ilkka
authors.initials: I
authors.lastname: Kunnamo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002908:Chronic Disease; D002985:Clinical Protocols; D020000:Decision Support Systems, Clinical; D064420:Drug-Related Side Effects and Adverse Reactions / Q000517:prevention & control*; D006801:Humans; D057970:Inappropriate Prescribing / Q000517:prevention & control*; D017063:Outcome Assessment, Health Care; D019338:Polypharmacy; D018401:Sample Size
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