The objective of this randomized controlled trial (RCT) is to evaluate whether the Systematic Tool to Reduce Inappropriate Prescribing (STRIP), put into practice through the STRIP Assistant (STRIPA) and implemented by general practitioners (GPs), will lead to an improvement in clinical and economic outcomes in patients aged 65 or older with multimorbidity and polypharmacy.

Background:

Policy makers face many challenges, when they plan health care systems to meet the needs of the fast growing elderly population. More than 60% of the elderly suffer from multiple chronic conditions (multimorbidity - commonly defined as ≥3 chronic diseases) and get multiple drugs (polypharmacy - commonly defined as ≥5 regular medications). Multimorbid patients are often excluded from randomized controlled trials (RCT) and consequently most prescribing guidelines address diseases in isolation. Consequently, there is inappropriate prescribing, which results in diminished health states and lower quality of life of the patients.

Older patients usually rely on their general practitioners (GPs) to manage their medications. However, GPs often have limited time to adapt polypharmacy. Reviewing medications and understanding their interactions based on a list of diagnoses and drugs is complex and time consuming. Furthermore, due to the increase of patients with multimorbidity and polypharmacy, medication review especially in patients with many drugs is often neglected. Pilot data from the Netherlands showed that a software-assisted method, called STRIPA, was effective for optimizing pharmacotherapy in primary care. Through the OPTICA trial this tool will now be tested in the Swiss primary care context.

Study design:

The OPTICA trial is a single-site cluster randomized controlled trial (RCT), which will be conducted at the Institute for Primary Health Care of the University of Bern (BIHAM). All study-related tasks will be performed centrally at the BIHAM except for patient recruitment and use of the STRIPA, as these two tasks will be performed in participating GP offices.

The GPs in the intervention group use the STRIP assistant, whereas the GPs in the control group conduct a sham intervention: usual medication review and shared-decision making with patient. STRIPA is designed to optimize drug therapy and to advise on safe and appropriate therapy using STOPP/START criteria (STOPP = 'screening tool of older people's prescriptions'; START = 'screening tool to alert to right treatment'). Patients will be followed for 1 year with follow-up phone calls after 6 and 12 months.

Study objectives:

The primary objective of this study is to assess the effect of pharmacotherapy optimization through STRIPA on the medication appropriateness, which is measured by the medication appropriateness index (MAI) for drug overuse and by the assessment of underutilization (AOU) for drug underuse.

The secondary objective of the OPTICA study is to assess the impact of pharmacotherapy optimization by STRIPA on the parameters listed below (1- 4) as well as to examine the use of the STRIP assistant by GPs (5) and to examine patients' willingness to deprescribe (6):

1. Degree of polypharmacy
2. Degree of over- and underprescribing
3. Number of falls and fractures
4. Quality of life, including pain/discomfort
5. Health economic parameters, including direct costs of the intervention and incremental cost-effectiveness
6. Enablers and barriers faced by GPs when using the STRIP assistant
7. Patients' willingness to deprescribe

Statistical considerations:

40 clusters with a cluster size of 8-10 patients will be included. The primary analysis will be an intention-to-treat (ITT) analysis, whereby all randomised patients will be included in the group they were allocated to.

There will be two co-primary outcomes, the improvement in the MAI score at 12 months, defined as decrease of the score of at least one point, and improvement in the AOU index at 12 months, defined as a reduction of at least one prescribing omission. Both outcomes will be tested separately and success claimed if either test is significant. Adjustment for multiple testing will be performed.

In the primary analysis, the investigators will assess outcomes at the patient level, accounting for the correlated nature of data among GPs by using multilevel mixed-effects models. For the co-primary outcomes, the investigators will present and compare the proportion of patients with improvement of the MAI score and AOU index in the control and intervention groups. The relative difference between groups will be assessed using a mixed-effects logistic model with a random intercept at the GP level in order to account for clustering.

Secondary binary outcomes will be evaluated like the primary outcomes. Secondary continuous outcomes will be analyzed using random-effects linear regression with a random intercept at the GP level. Models will additionally be adjusted for the baseline value as a covariate. Secondary count outcomes will be analyzed using random-effects Poisson regression with a random intercept at the GP level.

Health economic analyses will comprise the assessment i) of resource use and cost differences between the trial arms, ii) the assessment of differences in quality-adjusted lifetime between the trial arms (expressed as quality-adjusted life years [QALYs]), and iii) the assessment of the cost-effectiveness of the intervention in comparison with the comparator, i.e. medication review in accordance with standard care.

Inclusion Criteria

• Being a regular patient of participating GP
• Age: 65 years of age or older
• Multimorbidity: 3 or more coexistent chronic conditions defined by 3 distinct International Classification in Primary Care -2 (ICPC-2) codes defined as chronic (O'Halloran et al., 2004) with an estimated duration of 6 months or more, or based on a clinical decision supported by Pharmacost Groups (PCG) for chronic conditions in an algorithm from FIRE
• Polypharmacy: Use of five or more different regular drugs (defined as authorized medications with registration numbers) for more than 30 days before signing the informed consent form

Exclusion Criteria

• Inability to provide informed consent from a patient or to obtain informed consent from a proxy for patients with cognitive impairment
• If the patient is already participating in the a different interventional study

Data will be deposited in the Bern Open Repository and Information System (BORIS) (www.boris.unibe.ch). BORIS allows searching and is indexed by search engines.

All items are stored with a unique Digital Object Identifier (DOI) that can be referenced in respective publication.

The whole study database in csv format will be available and it will include readme files, metadata, information about the performed processing and analytical steps, variable definitions, and references to vocabularies used to help secondary users to understand and reuse the data.

Data will only be shared upon request to the sponsor-investigator. The data is owned by the sponsor-investigators. In case of data sharing, a data sharing agreement between the external party and the sponsor-investigator will need to be agreed on and signed.

The OPTICA study is partially blinded, with blinding being implemented as follows:

• Due to the nature of the study intervention participating GPs (care providers) cannot be blinded.
• Patients remain blinded. They will not be informed to which treatment arm their GP is allocated to, in order to minimize performance and other reporting biases. Despite this, they receive a "high-level description" of the study question and the study procedures.
• Data collection for primary and secondary outcome analyses will be conducted by blinded study team members.
• Outcome adjudication (MAI and AOU assessment) will be performed by blinded study team members.