Optimizing PharmacoTherapy In the Multimorbid Elderly in Primary CAre: the OPTICA Trial

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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): Degree of polypharmacy Degree of over- and underprescribing Number of falls and fractures Quality of life, including pain/discomfort Health economic parameters, including direct costs of the intervention and incremental cost-effectiveness Enablers and barriers faced by GPs when using the STRIP assistant 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.

Official Title
-----------------
Optimizing PharmacoTherapy In the Multimorbid Elderly in Primary CAre: a Cluster Randomized Controlled Trial (the OPTICA Trial)

Conditions
-----------------
Multimorbidity, Polypharmacy

Intervention / Treatment
-----------------
* Device: STRIPA intervention
* Other: Sham intervention


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Clusters will be randomized 1:1, to either the intervention arm receiving STRIPA or to the control arm undergoing a sham intervention. Each cluster is defined by one GP. The patients assigned to a cluster (i.e. GP) which was allocated to the intervention arm will undergo a systematic pharmacotherapy optimization by their GP using the STRIP assistant and shared decision making. Patients assigned to a cluster that was assigned to the control arm will receive a sham intervention, which consists of a usual medication review by the GP in accordance with usual care and shared decision making. This RCT randomizes GPs instead of patients to prevent contamination, which would occur if the same GPs treated patients in the intervention and the control arm simultaneously.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: STRIPA intervention<br>GPs in the intervention group will perform a STRIPA analysis for each of their 8-10 patients after the recruitment of the patient into the OPTICA trial, so that the results can be discussed in the next consultation and a shared decision-making can be performed. STRIPA is a structured method to perform pharmacotherapy optimization. The STRIPA intervention in the OPTICA trial consists of 4 steps: recording medication and diagnoses in STRIPA (upload from data from the 'Family medicine ICPC Research using Electronic medical records' (FIRE) database) structured drug review through the GP based on the STRIPA with the integrated STOPP/START criteria shared decision-making between GP and patient with possible adaptation of the recommendation follow-up through study team | Device: STRIPA intervention<br>* STRIPA is a Dutch software-based tool for the support of the pharmaceutical analysis by 1) taking into account the predictable adverse medication effects, 2) advising safe and appropriate therapy using established STOPP/START criteria, 3) interaction monitoring, and 4) appropriate dosing in accordance with renal function. It represents a highly efficient and user-friendly software engine, which is capable of individually screening the clinical status and pharmacological therapy of older patients with multimorbidity, which can define optimal drug therapy, and which can highlight the adverse drug reaction risk. A summary of these outputs will be used as STRIPA recommendations, which will, if applicable, be implemented by GPs and patients. Prior to the STRIPA medication review, the necessary patient information will be loaded from the FIRE database that contains data from more than 300 Swiss GP practices.<br>|
| Sham Comparator: Sham intervention<br>Patients in the control group will receive a sham intervention, which consists of a usual medication review by their GP as well as a shared decision making of the latter. | Other: Sham intervention<br>* Patients being assigned to the control arm will be treated in accordance with standard care. They will receive a sham intervention, which consists of a usual medication review by their GP and a shared decision making between patient and GP.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients' medication appropriateness, as measured by two complementary co-primary outcomes: Co-primary outcome #1: change in the Medication Appropriateness Index (MAI) | Medication Appropriateness Index (MAI), assessed at baseline as well as at the 6 and 12 months follow-ups for each chronic medication of the patient. The 10 item version of the MAI will be used, but the cost-effectiveness item will be excluded. The MAI score for each medication will range from 0 to 17. | 12 months | 
| Patients' medication appropriateness, as measured by two complementary co-primary outcomes: Co-primary outcome #2: change in the Assessment of Underutilization (AOU) | Assessment of Underutilization (AOU), assessed for each of the patients' chronic conditions at baseline as well as at the 6 and 12 months follow-ups. For each chronic condition of the patient, the assessors decided whether there is i) no omission, ii) marginal omission, or iii) omission of indicated medication. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients' degree of polypharmacy | Numbers of regular long-term medications taken by patients, assessed at baseline as well as the 6 and 12 months follow-ups. | 12 months | 
| Patients' degree of overprescribing, as measured by the Medication Appropriateness Index (MAI) | The degree of overprescribing be assessed at baseline as well as at the 6 and 12 months follow-ups. The 10 item version of the MAI will be used. The MAI score for each medication will range from 0 to 18. | 12 months | 
| Patients' degree of underprescribing, as measured by the Assessment of Underutilization | The degree of underprescribing will be assessed at baseline as well as at the 6 and 12 months follow-ups. For each chronic condition of the patient, the assessors decided whether there is i) no omission, ii) marginal omission, or iii) omission of indicated medication. | 12 months | 
| Patients' falls and fractures | Number of falls and fractures reported by the patients. Assessed at baseline as well as at the 6 and 12 months follow-ups. | 12 months | 
| Patients' quality of life measured by 5-level version of the European Quality of Life-5 Dimensions questionnaire (EQ-5D), including pain/discomfort. | Assessed by the 5-level version of the European Quality of Life - 5 Dimensions questionnaire (EQ-5D). Assessed at baseline as well as at the 6 and 12 months follow-ups. The questionnaire consists of 5 questions with 5 possible responses each and a visual analogue scale (0-100). The EQ-5D-5L index resulting from this questionnaire ranges from 0 to 1. | 12 months | 
| Amount of formal care received by patients | Assessed by looking at number of planned and unplanned care sessions received by a patient. Assessed at baseline as well as at the 6 and 12 months follow-ups. | 12 months | 
| Amount of informal care received by patients | Assessed by looking at unpaid care by e.g. family members, relatives, friends. Assessed at baseline as well as at the 6 and 12 months follow-ups. | 12 months | 
| Survival | As measured by number of survivors | 12 months | 
| Patients' Quality-adjusted life years (QALYs) | Assessment will be done at the end of the trial, when all data was collected. | 12 months | 
| Patients' medical costs | Direct medical costs during one year. Assessment will be done at the end of the trial, when all data was collected. | 12 months | 
| Cost-effectiveness of the STRIPA intervention | The cost-effectiveness analysis will be performed by combining clinical data, quality of life data as well as data about the amount of formal and informal care collected within the trial, and unit costs that will stem from external sources. | 12 months | 
| Percentage of recommendations accepted by general practitioners (GPs) | Quantification of the amount of recommendations generated by the STRIP assistant that have been accepted by GPs. Assessed after all the GPs in the intervention group have used the STRIPA. | 12 months | 
| Percentage of recommendations rejected by general practitioners (GPs) | Quantification of the amount of recommendations generated by the STRIP assistant that have been rejected by GPs. Assessed after all the GPs in the intervention group have used the STRIPA. | 12 months | 
| Patient's willingness to deprescribe | The willingness of patients' to deprescribe will be assessed by the revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire. Assessed at baseline. The score will range from 0 to 22 for the patient questionnaire and between 0 and 19 for the caregiver questionnaire. | Baseline | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Drug utilization review, Old age