Deprescribing Trials: Methods to Reduce Polypharmacy and the Impact on Prescribing and Clinical Outcomes

Polypharmacy is prevalent in older adults with cancer and associated with multiple adverse outcomes. A single-site, cluster-randomized clinical trial will enroll older adults with cancer and polypharmacy starting chemotherapy and will assess the effectiveness and feasibility of deprescribing interventions by comparing two arms: a pharmacist-led deprescribing intervention and a patient educational brochure.

The study will be conducted in two phases. In phase I, focus groups and semi-structured individual interviews will guide adaptation of deprescribing interventions for the oncology clinic (phase Ia), and eight patients will undergo the pharmacist-led deprescribing intervention with iterative adaptations (phase Ib). In phase II, a pilot cluster-randomized trial (n = 72) will compare a pharmacist-led deprescribing intervention with a patient education brochure, with treating oncologists as the cluster. Both efficacy (relative dose intensity of planned chemotherapy, potentially inappropriate medications successfully deprescribed, chemotherapy toxicity, functional status, hospitalizations, falls, and symptoms) and implementation outcomes (barriers and facilitators) will be assessed.

This study is anticipated to provide pilot data to inform a nationwide randomized clinical trial of deprescribing in older adults starting cancer treatment. The cluster randomization is intended to provide an initial estimate for the intervention effect as well as oncologists' intra-class correlation coefficient. Deprescribing interventions may improve outcomes in older adults starting cancer treatment, but these interventions are understudied in this population, and it is unknown how best to implement them into oncology practice. The results of this trial will inform the design of large, randomized phase III trials of deprescribing.

ClinicalTrials.gov Identifier: NCT05046171. Date of registration: September 16, 2021.

The 6th APV (Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnologie e.V., The International Association for Pharmaceutical Technology) Winter Conference took place in Salzburg (Austria) from January 19–20, 2023. This conference was dedicated to advance patient-centric drug development across all dosage forms, indications and patient populations and was organized by the APV PaCeMe IN Task Force. The topic was chosen due to emerging evidence and increasing regulatory requirements to consider patient needs and capabilities in drug product development. It is well acknowledged that acceptability of a drug product and its dosage form is a fundamental aspect of patient centric drug product design which can directly impact adherence and intended use, hence effectiveness and safety. Despite the requirement to proof acceptability within the drug development program, respective methods to determine and compare the degree of acceptability of different dosage forms and drug product designs are still limited.

Deprescribing is a patient-centered approach to managing inappropriate polypharmacy that faces several barriers, including patients' attitudes and beliefs about medications that need to be considered. For this purpose, the revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire is a helpful instrument, but until now, there is no Portuguese version.

To translate and validate the rPATD questionnaire (older adults version) to Portuguese.

The rPATD questionnaire was translated and cross-culturally adapted using forward-backward translation and pre-testing. A cross-sectional study with 192 older adults aged ≥65 years taking at least 1 regular medication was conducted for validity assessment. Participants were recruited by convenience sampling in 3 Portuguese outpatient rehabilitation medicine clinics. Psychometric properties were evaluated through face and content validity; construct validity, by assessing structural validity through exploratory factor analysis, hypotheses testing, including concurrent validity and cross cultural validity; reliability with internal consistency; and item-total correlation. Floor and ceiling effects were examined.

The exploratory factor analysis (EFA) revealed a 4-factor structure that explains 51.08% of the total variance, as in the original rPATD. These 4 factors are related to the level of involvement in medication management, beliefs in the appropriateness of medication, perceived burden of medication, and concerns about stopping medications. Factor loadings ranged from 0.226 to 0.800; 2 items scored <0.3, and no cross-loading was found. The exclusion of the 2 items loading <0.3 in the EFA showed no significant improvement in factor loading or internal consistency, so the item structure was maintained. In hypothesis testing, 78% of the correlations were correctly predicted. The 4 factors internal consistency was generally acceptable, with Cronbach's alpha ranging from 0.638 to 0.830. The item-total correlation ranged between 0.223 and 0.7.

The Portuguese rPATD questionnaire for older adults presents globally good or acceptable psychometric properties.

For patients with geriatric frailty, reducing inappropriate medication is an important goal to improve patient safety in primary care. GP-side barriers include knowledge gaps, legal concerns, and lack of communication between the actors involved. The aim was to develop a multi-faceted intervention to facilitate deprescribing and shared prioritisation among frail elderlies with polypharmacy living at home.

Mixed methods study including: 1) scoping review on family conferences, expert panels; 2) group discussions with GPs, mapping of needs and challenges in Primary Care; 3) workshops and expert interviews with GPs, patient advocates, researchers as a basis for a theoretical intervention model; 4) piloting.

A major challenge for GPs is to conduct a productive discussion with patients and family cares on deprescribing and drug safety. A guideline for a structured family conference with a medication check and geriatric assessment was developed and proved to be feasible in the pilot study.

The intervention developed to facilitate deprescribing and shared prioritisation of drug therapy based on family conferences seems suitable to be tested in a subsequent cRCT.

Adapting family conferences to primary care for frail patients with polypharmacy.

The first Danish symposium on evidence-based deprescribing was held in September 2019. The symposium aimed to increase the awareness of deprescribing in general, to discuss the importance of deprescribing, and, thus, a potential consensus on key issues on a national deprescribing agenda. The invited keynote speaker, Barbara Farrell, from the Bruyére Research Institute, Ottawa, Canada, presented their thorough work on deprescribing guideline development and application. The symposium consisted of two parts: Part 1 concentrated on establishing the need for deprescribing in our society. Part 2 consisted of a panel debate that put the practical application and implementation of deprescribing in perspective to the input from the audience and the structure of the Danish healthcare system. The panelists represented key stakeholders, e.g., clinical pharmacists, general practitioners, hospital doctors, Danish Health Authority representatives, health politicians concerning deprescribing in Denmark. The event allowed 145 participants to discuss the importance of implementing deprescribing in a Danish setting. This commentary highlights and discusses the major themes that characterized the symposium: “why deprescribe?”, “deprescribing research” and a theme dedicated to “problems of concern.” The emergence of these themes formed the basis for the discussion of new strategies and a proposal for a future gold standard to succeed in deprescribing.

Recent work over the past several decades has identified the key molecular “hallmarks of aging.” These discoveries have paved the way for novel lifestyle and pharmacological strategies for improving human health span. However, not all therapies are likely to work for every person. The most effective strategies for improving human healthspan will likely come from the convergence of two rapidly emerging fields of study: GeroScience—devoted to understanding the molecular mechanisms of aging in order to slow its progression, and Personalized Medicine—devoted to creating tailored treatments based on individual patient characteristics. This chapter will focus on the potential of personalized medicine for creating individualized treatments for preventing or reversing the biological mechanisms of aging.