Methods for evaluating the benefit and harms of deprescribing in observational research using routinely collected data

Deprescribing is defined as “the planned and supervised process of dose reduction or stopping of medication that might be causing harm, or no longer be of benefit”. Barriers to deprescribing include healthcare professional fear and lack of guidance. These may stem from limited available evidence on benefits and harms of deprescribing medications commonly used among older persons. Advances in pharmacoepidemiology and causal inference methods to evaluate comparative effectiveness and safety of prescribing medications have yet to be considered for deprescribing medication. This paper discusses select methods and how they can be applied to deprescribing research, using case studies of benzodiazepines and low-dose acetylsalicylic acid (aspirin). Target trial emulation involves the explicit application of design principles from randomised controlled trials to observational studies. Several design aspects, including defining eligibility criteria and time zero, require additional considerations for deprescribing studies. The active comparator new user design also presents challenges, including selection of an appropriate comparator. This paper discusses these aspects, and others, in relation to deprescribing studies. Furthermore, methods proposed to control for confounding, in particular, the prior event rate ratio and propensity scores, are discussed. Introduction of billing codes or mechanisms for accurately determining when deprescribing has occurred would enhance the ability to conduct research using routinely collected data. Although the approaches discussed in this paper may strengthen observational studies of deprescribing, their use may be best suited to certain scenarios or research questions, where randomised controlled trials may be less feasible

Methodology for Developing Deprescribing Guidelines: Using Evidence and GRADE to Guide Recommendations for Deprescribing

<div><p>Background</p><p>Class specific deprescribing guidelines could help clinicians taper and stop medications no longer needed or which may be causing more harm than benefit. We set out to develop methodology to create such guidelines using evidence-based methods for guideline development, evidence synthesis and recommendation rating.</p><p>Methods and Findings</p><p>Using a comprehensive checklist for a successful guideline enterprise, we conducted a national modified Delphi consensus process to identify priorities for deprescribing guidelines, then conducted scoping exercises to identify feasible topics, and sequentially developed three deprescribing guidelines. We selected guideline development team members for clinical expertise; a GRADE member worked with staff to ensure guideline development processes were followed. We conducted or used systematic searches and reviews of deprescribing trials of selected drug classes, reviews or systematic reviews of drug class effectiveness, reviews of reviews of drug class harm and narrative syntheses of contextual questions to inform recommendations and guideline development. Our 8 step process for guideline development included defining scope and purpose, developing a logic model to guide the process and generate key clinical questions, setting criteria for admissible evidence and conducting systematic reviews, synthesizing evidence considering additional contextual information and performing quality estimates, formulating recommendations and providing strength estimations, adding clinical considerations, conducting clinical and stakeholder review and finally updating content pre-publication. Innovative aspects of the guideline development process included synthesizing evidence for outcomes of tapering or stopping medication, and incorporating evidence for medication harm into the recommendation strength rating. Through the development of three deprescribing guidelines (for proton pump inhibitors, benzodiazepine receptor agonists and antipsychotics) and associated decision-support algorithms, we were able to gradually hone the methodology; each guideline will be published separately.</p><p>Conclusion</p><p>Our methodology demonstrates the importance of searching for short and long-term outcomes, showing the benefits of deprescribing and studying patient preferences. This publication will support development of future deprescribing guidelines.</p></div

Sample clinical consideration questions.

<p>Sample clinical consideration questions.</p

Generic Deprescribing Logic Model.

<p>Generic Deprescribing Logic Model.</p

Overall methodology for deprescribing guideline preparation, development, implementation and revision.

<p>Overall methodology for deprescribing guideline preparation, development, implementation and revision.</p

Steps used to develop deprescribing guidelines.

<p>Steps used to develop deprescribing guidelines.</p

Ten deprescribing articles you should know about: A guide for newcomers to the field

Deprescribing is the planned and supervised process of stopping a medication when that medication may no longer be necessary, is causing more harm than good or does not align with a person's healthcare goals and treatment preferences. There has been an explosion of deprescribing research published over the last 10 years. Researchers in the field have been doing everything from evaluating deprescribing rates in usual care to studying barriers and facilitators around establishing deprescribing in routine clinical practice. More recently, interventions specifically designed to intervene on major determinants of deprescribing have been developed and tested. For someone new to the field (e.g., researchers new to the field, trainees or clinicians interested in learning more about deprescribing research), it might be difficult to know where to begin in order to gain a solid grasp of the deprescribing literature. At the 1st International Conference on Deprescribing, held in Denmark in September 2022, this author group discussed which deprescribing articles represented work that collectively provides a diverse overview of the field for newcomers. We hoped such a collection of articles would provide an overview of the breadth of work in this area and highlight seminal pieces that shaped the field. We were inspired by the success of similar lists in related fields1 and previous discussions on social media. Our group of deprescribing experts (n = 8) first generated a preliminary list of 31 possible articles, from which we aimed to narrow down to a final 10. We tasked ourselves with thinking about articles that covered a broad range of topics in the field and articles that had the following characteristics: high impact on the field, high-level articles (such as reviews, which could provide broad overview of research on a specific topic) or studies that incorporated novel approaches. Once we generated a preliminary list, we sent out a survey asking the eight authors “Should this article be in the Top 10?” for the 31 candidate articles. We tallied the “Yes” votes, and the 10 articles with the most “Yes” votes were included in the final list (Table 1). We created the following categories to group the articles under after the 10 were identified: “Critical concepts,” “High level overviews,” “Major trials,” “The complexity of deprescribing” and “Knowledge synthesis in deprescribing.” There are some articles that did not make the Top 10 that some of us still felt strongly were useful for newcomers to know about. These articles offer additional insight into important concepts in the field such as design of deprescribing interventions,2 countering cognitive biases related to deprescribing3 and the consequences of polypharmacy.4 Newcomers may also want to be aware of landmark trials that have tested novel deprescribing concepts or interventions,5-7 as well as the recent focus on implementation science in the field of deprescribing,8 and the influence of health system factors on deprescribing implementation and success.9 We recognize that this list is not exhaustive by any means and is based on the opinions of a group of established researchers in the field. It is not a comprehensive list of all the important deprescribing articles. However, it provides a start-up kit for newcomers wondering “where to start.”</p

Deprescribing: future directions for research

A World Café workshop was held at the Bruyère Evidence-Based Deprescribing Guidelines Symposium in March 2018 with 30 participants (researchers, clinicians, policy makers, stakeholders). This workshop explored priorities for future work in the field of deprescribing and deprescribing guidelines through group discussion. The discussions were guided by the following questions: (1) What are deprescribing research priorities (to inform guideline development), (2) What outcome measures are important for developing deprescribing guidelines, and (3) How do we evaluate the implementation and effectiveness of deprescribing guidelines? Discussion from all 3 questions identified 6 main priority areas: (1) conducting high-quality and long-term clinical trials that measure patient-important outcomes, (2) focusing on patient involvement and perspectives, (3) investigating the pharmacoeconomics of deprescribing interventions, (4) understanding deprescribing interventions in different populations, (5) generating evidence on clinical management during deprescribing (e.g. managing adverse drug withdrawal effects, subsequent re-prescribing), and (6) implementing interventions in clinical practice. These topics represent what a group of experienced researchers, clinicians, and stakeholders in the field collectively felt was important to consider for design and implementation of future deprescribing studies. The aim is for these findings to stimulate future discussions and be considered by granting agencies, policy makers, deprescribing research networks, and individual researchers planning future deprescribing studies

Lack of Evidence to Guide Deprescribing of Antihyperglycemics: A Systematic Review

<p><strong>Article full text</strong></p> <p><br> The full text of this article can be found <a href="https://link.springer.com/article/10.1007/s13300-016-0220-9"><b>here</b>.</a><br> <br> <strong>Provide enhanced digital features for this article</strong><br> If you are an author of this publication and would like to provide additional enhanced digital features for your article then please contact <u>[email protected]</u>.<br> <br> The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.<br> <br> Other enhanced features include, but are not limited to:<br> • Slide decks<br> • Videos and animations<br> • Audio abstracts<br> • Audio slides<u></u></p> <p> </p> <p> </p> <p> </p

Deprescribing guidelines: an international symposium on development, implementation, research and health professional education

Deprescribing is a clinically important and feasible innovation that ensures medication efficacy, reduces harms, and mitigates polypharmacy. It involves reducing doses or stopping medications that are not useful, no longer needed, or which may be causing harm. It may also involve changing to a safer agent or using non-pharmacological approaches for care instead. Clinical guidelines combined with behaviour changes (of health care providers (HCPs), the public, and health care decision-makers) are needed to integrate deprescribing into routine practice. Using rigorous international standards, the Bruyère Research Institute Deprescribing Guidelines research team validated a ground-breaking deprescribing guideline methodology and developed or co-developed 5 evidence-based deprescribing guidelines. In March 2018, the team hosted an international symposium convening HCPs, researchers, public agencies, policymakers, and patient advocates in Ottawa, Ontario, Canada. This 3-day symposium aimed to facilitate knowledge exchange amongst guideline developers, users, and the public; initiate partnerships and collaborations for new deprescribing guideline recommendations and effectiveness research; and to continue work on HCP deprescribing education activities. An interprofessional planning committee developed an overall agenda, and small groups worked on session objectives and formats for different components: methods for rigorous deprescribing guideline development, implementation experiences, research/evaluation experiences and educational needs. Through a series of keynote speakers, panel discussions, and small working groups, the symposium provided a forum for participants to meet one another, learn about their different experiences with deprescribing guidelines, and develop collaborations for future initiatives. One hundred thirty participants, from 10 countries and representing over 100 institutions and organizations took part. Symposium proceedings are presented in this issue of RSAP for sharing with the wider community engaged in the care of patients with problematic polypharmacy