Pilot study to test the feasibility of a trial design and complex intervention on PRIoritising MUltimedication in Multimorbidity in general practices (PRIMUMpilot).

To improve medication appropriateness and adherence in elderly patients with multimorbidity, we developed a complex intervention involving general practitioners (GPs) and their healthcare assistants (HCA). In accordance with the Medical Research Council guidance on developing and evaluating complex interventions, we prepared for the main study by testing the feasibility of the intervention and study design in a cluster randomised pilot study. 20 general practices in Hesse, Germany. 100 cognitively intact patients ≥65 years with ≥3 chronic conditions, ≥5 chronic prescriptions and capable of participating in telephone interviews; 94 patients completed the study. The HCA conducted a checklist-based interview with patients on medication-related problems and reconciled their medications. Assisted by a computerised decision-support system (CDSS), the GPs discussed medication intake with patients and adjusted their medication regimens. The control group continued with usual care. Feasibility of the intervention and required time were assessed for GPs, HCAs and patients using mixed methods (questionnaires, interviews and case vignettes after completion of the study). The feasibility of the study was assessed concerning success of achieving recruitment targets, balancing cluster sizes and minimising drop-out rates. Exploratory outcomes included the medication appropriateness index (MAI), quality of life, functional status and adherence-related measures. MAI was evaluated blinded to group assignment, and intra-rater/inter-rater reliability was assessed for a subsample of prescriptions. 10 practices were randomised and analysed per group. GPs/HCAs were satisfied with the interventions despite the time required (35/45 min/patient). In case vignettes, GPs/HCAs needed help using the CDSS. The study made no patients feel uneasy. Intra-rater/inter-rater reliability for MAI was excellent. Inclusion criteria were challenging and potentially inadequate, and should therefore be adjusted. Outcome measures on pain, functionality and self-reported adherence were unfeasible due to frequent missing values, an incorrect manual or potentially invalid results. Intervention and trial design were feasible. The pilot study revealed important limitations that influenced the design and conduct of the main study, thus highlighting the value of piloting complex interventions. ISRCTN99691973; Results.

Muth C ，Harder S ，Uhlmann L ，Rochon J ，Fullerton B ，Güthlin C ，Erler A ，Beyer M ，van den Akker M ，Perera R ，Knottnerus A ，Valderas JM ，Gerlach FM ，Haefeli WE ... -  《BMJ Open》

Effectiveness of a complex intervention on Prioritising Multimedication in Multimorbidity (PRIMUM) in primary care: results of a pragmatic cluster randomised controlled trial.

Investigate the effectiveness of a complex intervention aimed at improving the appropriateness of medication in older patients with multimorbidity in general practice. Pragmatic, cluster randomised controlled trial with general practice as unit of randomisation. 72 general practices in Hesse, Germany. 505 randomly sampled, cognitively intact patients (≥60 years, ≥3 chronic conditions under pharmacological treatment, ≥5 long-term drug prescriptions with systemic effects); 465 patients and 71 practices completed the study. Intervention group (IG): The healthcare assistant conducted a checklist-based interview with patients on medication-related problems and reconciled their medications. Assisted by a computerised decision support system, the general practitioner optimised medication, discussed it with patients and adjusted it accordingly. The control group (CG) continued with usual care. The primary outcome was a modified Medication Appropriateness Index (MAI, excluding item 10 on cost-effectiveness), assessed in blinded medication reviews and calculated as the difference between baseline and after 6 months; secondary outcomes after 6 and 9 months' follow-up: quality of life, functioning, medication adherence, and so on. At baseline, a high proportion of patients had appropriate to mildly inappropriate prescriptions (MAI 0-5 points: n=350 patients). Randomisation revealed balanced groups (IG: 36 practices/252 patients; CG: 36/253). Intervention had no significant effect on primary outcome: mean MAI sum scores decreased by 0.3 points in IG and 0.8 points in CG, resulting in a non-significant adjusted mean difference of 0.7 (95% CI -0.2 to 1.6) points in favour of CG. Secondary outcomes showed non-significant changes (quality of life slightly improved in IG but continued to decline in CG) or remained stable (functioning, medication adherence). The intervention had no significant effects. Many patients already received appropriate prescriptions and enjoyed good quality of life and functional status. We can therefore conclude that in our study, there was not enough scope for improvement. ISRCTN99526053. NCT01171339; Results.

Muth C ，Uhlmann L ，Haefeli WE ，Rochon J ，van den Akker M ，Perera R ，Güthlin C ，Beyer M ，Oswald F ，Valderas JM ，Knottnerus JA ，Gerlach FM ，Harder S ... -  《BMJ Open》

Activating GENeral practitioners dialogue with patients on their Agenda (MultiCare AGENDA) study protocol for a cluster randomized controlled trial.

Altiner A ，Schäfer I ，Mellert C ，Löffler C ，Mortsiefer A ，Ernst A ，Stolzenbach CO ，Wiese B ，Scherer M ，van den Bussche H ，Kaduszkiewicz H ... -  《BMC Family Practice》

Supporting prescribing in older people with multimorbidity and significant polypharmacy in primary care (SPPiRE): a cluster randomised controlled trial protocol and pilot.

McCarthy C ，Clyne B ，Corrigan D ，Boland F ，Wallace E ，Moriarty F ，Fahey T ，Hughes C ，Gillespie P ，Smith SM ... -  《Implementation Science》

'Optimising PharmacoTherapy In the multimorbid elderly in primary CAre' (OPTICA) to improve medication appropriateness: study protocol of a cluster randomised controlled trial.

Multimorbidity and polypharmacy are major risk factors for potentially inappropriate prescribing (eg, overprescribing and underprescribing), and systematic medication reviews are complex and time consuming. In this trial, the investigators aim to determine if a systematic software-based medication review improves medication appropriateness more than standard care in older, multimorbid patients with polypharmacy. Optimising PharmacoTherapy In the multimorbid elderly in primary CAre is a cluster randomised controlled trial that will include outpatients from the Swiss primary care setting, aged ≥65 years with ≥three chronic medical conditions and concurrent use of ≥five chronic medications. Patients treated by the same general practitioner (GP) constitute a cluster, and clusters are randomised 1:1 to either a standard care sham intervention, in which the GP discusses with the patient if the medication list is complete, or a systematic medication review intervention based on the use of the 'Systematic Tool to Reduce Inappropriate Prescribing'-Assistant (STRIPA). STRIPA is a web-based clinical decision support system that helps customise medication reviews. It is based on the validated 'Screening Tool of Older Person's Prescriptions' (STOPP) and 'Screening Tool to Alert doctors to Right Treatment' (START) criteria to detect potentially inappropriate prescribing. The trial's follow-up period is 12 months. Outcomes will be assessed at baseline, 6 and 12 months. The primary endpoint is medication appropriateness, as measured jointly by the change in the Medication Appropriateness Index (MAI) and Assessment of Underutilisation (AOU). Secondary endpoints include the degree of polypharmacy, overprescribing and underprescribing, the number of falls and fractures, quality of life, the amount of formal and informal care received by patients, survival, patients' quality adjusted life years, patients' medical costs, cost-effectiveness of the intervention, percentage of recommendations accepted by GPs, percentage of recommendation rejected by GPs and patients' willingness to have medications deprescribed. The ethics committee of the canton of Bern in Switzerland approved the trial protocol. The results of this trial will be published in a peer-reviewed journal. Swiss National Science Foundation, National Research Programme (NRP 74) 'Smarter Healthcare'. Clinicaltrials.gov (NCT03724539), KOFAM (Swiss national portal) (SNCTP000003060), Universal Trial Number (U1111-1226-8013).

Jungo KT ，Rozsnyai Z ，Mantelli S ，Floriani C ，Löwe AL ，Lindemann F ，Schwab N ，Meier R ，Elloumi L ，Huibers CJA ，Sallevelt BTGM ，Meulendijk MC ，Reeve E ，Feller M ，Schneider C ，Bhend H ，Bürki PM ，Trelle S ，Spruit M ，Schwenkglenks M ，Rodondi N ，Streit S ... -  《BMJ Open》