Health professionals’ and researchers’ opinions on conducting clinical deprescribing trials

Abstract While clinical deprescribing trials are increasingly being performed, there is no guidance on the optimum conduction of such studies. The aim of this survey was to explore the perspectives, attitudes, interests, barriers, and enablers of conducting clinical deprescribing trials among health professionals and researchers. An anonymous survey was developed, reviewed, and piloted by all investigators and informed by consultation with experts, as well as current deprescribing guidelines. The questions were formulated around current clinical trial frameworks and incorporated identified enablers and barriers of performing deprescribing studies. The survey was sent to members of Australian and international deprescribing, pharmacological, and pharmacy organizations, and other researchers published in deprescribing. A total of 96 respondents completed the survey (92.3% completion rate). Respondents indicated the main deprescribing trial rationale is to generate evidence to optimize patient‐centered outcomes (79.2%). Common barriers identified included the time and effort required (18.2%), and apprehension of health professionals involved in trials (17.1%). Studies are enabled by positive attitudes toward deprescribing of treating prescribers (24.4%) and patients (20.9%). Classical randomized controlled trials (RCTs) were deemed the most appropriate methodology (93.2%). Sixty percent of participants indicated a good clinical practice framework is required to guide the conduct of deprescribing trials. There were no significant differences in responses based on previous experience in conducting clinical deprescribing trials. In conclusion, clinical deprescribing trials should be conducted to investigate whether deprescribing medications improves patient care. A future deprescribing trial framework should use classical RCTs as a model, ensure participant safety, and target patient‐centered outcomes.


| INTRODUC TI ON
Deprescribing has been identified as the patient-centered process of withdrawing potentially harmful or unnecessary medications in order to improve health outcomes. 1 Despite many deprescribing studies being in progress internationally, there is an ongoing recognition of the need to conduct quality, robust clinical deprescribing trials to investigate the benefits and safety of stopping medicines. [2][3][4] However, study design and outcomes often vary, leading to great heterogeneity in the literature, and presenting challenges for researchers and practitioners to synthesize results and implement recommendations into clinical practice. [5][6][7][8] The primary challenge in deprescribing research is the weighing of risks the patient may accept against the potential benefits of discontinuing a drug. 9 The recognition of more information on appropriate medication use has been highlighted by the World Health Organization, who have established Medication Without Harm as the theme of the third Global Patient Safety Challenge, with an overall goal of reducing severe avoidable medication-harm by 50% globally. 10 To improve the knowledge on the safety of deprescribing, researchers and health professionals have called for more high-quality evidence, requiring more clinical deprescribing trials. [11][12][13] Definitive clinical deprescribing trials would not only inform on the safety of deprescribing but also provide guidance on assessment of relevant outcomes.
While there are international clinical deprescribing guidelines, there is no Consolidated Standards of Reporting Trials (CONSORT) extension nor recognized framework for conducting clinical deprescribing trials. 11,[13][14][15][16][17] Furthermore, while numerous studies have examined the perspectives on deprescribing from health professionals and patient groups, only one has explored the perspectives of those individuals who conduct the deprescribing trials. 5,12,[18][19][20][21][22][23][24][25][26] However, this study only gathered the opinions of a selected group of researchers and health professionals in a research workshop setting, and did not systematically analyze the ideas brought forward to evaluate their recommendations. 12,24 Instead a World Café, open dialogue session with roundtable discussion, was used with three questions on: research priorities for developing; outcome measures to inform; and, how to evaluate the implementation of, deprescribing guidelines in clinical settings. 12,24 Nor did this study examine other themes specific to clinical trials such as participant recruitment, ethical approval barriers, or the most appropriate study design.
Given that increasing numbers of deprescribing trials are currently being conducted, direction is needed on their design, conduct, and reporting. 27 Yet, at present, there is little data on health professionals' and researchers' perspectives and experiences about conducting deprescribing clinical trials.

| AIM
To determine the perspectives, attitudes, interests, and perceived barriers and enablers in relation to conducting clinical deprescribing trials among health professionals and researchers.

| Design
An anonymous, online survey was created using Research Data Electronic Capture (REDCap) software hosted on University of Sydney servers, and consisted of a nonrandomized mix of multiple- choice questions and open-ended options.
Twelve questions were developed, reviewed and piloted by all investigators for content validity. In addition, we sought input on questionnaire content from key national (n = 2) and international (n = 2) experts with experience in conducting deprescribing trials. The questions were formulated based on current clinical trial frameworks and addressed themes identified as barriers and enablers in current literature. 15

| Participants
A letter of invitation with the closed survey link was sent by email to members of international deprescribing, and polypharmacy and pharmacy organizations including: Canadian Deprescribing Network

| Analysis of results
Anonymous data from the Research Electronic Data Capture Data were reported as descriptive statistics and presented as mean, number of responses, and percentage. The data from the openended questions were derived using thematic analysis with themes derived using summative content analysis. 29 Respondents were invited to identify three key components of a future framework, or to state three reasons why a future framework is not required. Study sample size was taken as the number of respondents who answered at least the first question following demographic data, irrespective of if all questions were answered or not.

| RE SULTS
Cookie data collected by REDCap indicated there were 117 unique site visitors with 104 respondents completing the baseline data (88.9% participation rate), and 96 completing at least one survey question (92.3% completion rate). Of these, 84 respondents submitted the completed survey with all questions answered ( Figure 1).
The mean age of respondents was 45.0 (SD ± 11.6), and majority was female (54.3%) ( Table 1). Canada was the most popular base for respondents (31.7%), and most respondents were academics (34.7%). Less than half (41.3%) of respondents indicated that they had previous experience in conducting clinical deprescribing trials.
There were no significant differences between responses to all questions based on participants' previous experience in conducting clinical deprescribing trials.

| Rationale, barriers, and enablers of conducting clinical deprescribing trials
In relation to survey sample size, 96 respondents completed at least one question and respondents could submit more than one response or skip questions giving different sample sizes for each question.
The first three questions explored the rationale, and common barriers and enablers of conducting clinical deprescribing trials (Table 2). Respondents overwhelmingly indicated that the primary rationale for deprescribing studies is to "optimise clinical and/or patient centered outcomes" (79.2 ± 8.1%). Common enablers to conducting trials were "the beliefs of other health professionals regarding benefits of deprescribing" (24.4%), and "willingness of patients to participate" (20.9%). Common barriers to completing trials were the "time and effort required" (18.2%), and "establishing and/ or maintaining relationships with other health professionals" (17.1%).

| Pretrial approval and participant recruitment barriers
In seeking ethical approval for deprescribing trials ( Note: Participants were able to select more than one option for barriers and enablers; N = 96.

| Appropriateness of clinical trial methodologies and participant recruitment sites
In determining appropriate study methodologies and sites ( Figure 2

| Potential need for future framework and CONSORT list amendment
Finally, respondents were asked if they believed a "legal, regulatory and good clinical practice framework" needed to be developed for clinical deprescribing trials, and whether the CONSORT list required amending to include deprescribing trials ( Figure 3). Most respondents indicated that a good clinical practice framework did need to be developed (60.0 ± 11.0%), but that the current CONSORT list did not need amending (38.9% yes ± 11.6%). There was greater resist- Note: Participants could select more than one option; N = 96.

| D ISCUSS I ON
To our knowledge, this is the first study that has systematically in-  The primary concern reported by health professionals regarding deprescribing is safety. 5,12,18,[20][21][22]25 Ensuring patient safety should be the primary factor in influencing any decision made by a treating clinician-but often there is uncertainty on what deprescribing involves and its potential benefits; especially in vulnerable patient groups. 12 These vulnerable patient groups, including those "where consent must be acquired through a proxy", and those who "transition through various healthcare settings", were recognized as the most difficult patients to enroll and retain in clinical deprescribing trials (39.5% and 44.2%, respectively). This challenge extends to when institutional ethical approval is sought, with the most commonly identified barrier being the recruitment of "vulnerable participants", and those "unable to provide… consent" (18.9% and 18.5%, respectively).
Previous studies, however, have demonstrated that patients, while having strong preexisting attitudes toward drug use, are willing to cease treatments if there may be a positive health benefit, they can reduce their drug burden, and it is deemed appropriate by their doctor. 19,23,26 This is reflected with the strong response on the "willingness of patients to participate" (20.9%) as an enabler in conducting clinical deprescribing trials. Indeed, a recent study concluded that older adults generally fall into three categories regarding attitudes toward drugs and overall opinions on deprescribing: type 1 who are positive toward drugs and leave decisions to their doctors; type 2 who are more proactive and open to deprescribing; and type 3 who are generally frail and defer decisions to their doctor or caregiver. 26 To utilize these beliefs, and ensure adequate participant recruitment, patients, and care givers, must be presented with evidence on the potential benefits of deprescribing, and how patient safety will be ensured.
To overcome prescribers' and participants' fears, a rigorous trial methodology must be practiced and respondents strongly in-

| Strengths and limitations
The main strength was that this survey was informed by interna- was not possible to determine the exact response rate from the due to not knowing how many potential participants received the survey within each organization mailing list.
In conclusion, researchers and health professionals had a variety of opinions on conducting clinical deprescribing trials with some key themes emerging. Our findings suggest that deprescribing trials should be conducted to optimize patient-centered outcomes with health professional engagement of paramount importance to ensure the conduct of a clinical deprescribing trial and enable evidence synthesis across trials. Future studies should ideally establish a clinical deprescribing trial framework with RCTs as a model, which emphasizes monitoring safe clinical practice at all stages and targets patient-centered outcomes. The findings and recommendations of this study could also be presented to other health care professionals not engaged in deprescribing, to gather their opinions on conducting clinical deprescribing trials and inform future researchers.

D I SCLOS U R E
There are no competing interests to declare.

AUTH O R S' CO NTR I B UTI O N S
AJC designed, revised, and distributed the survey, monitored data for the whole trial, wrote the statistical analysis plan, collected, cleaned and analyzed the data, and drafted and revised the paper.
He is the guarantor. DG designed, revised and distributed the survey, monitored data collection, analyzed the data, and revised the paper.
SNH revised the survey, analyzed the data, and revised the paper. LK revised the survey, analyzed the data, revised the statistical analysis plan, and revised the paper. SLN revised the paper.