Assessing the feasibility of the Effectiveness of Discontinuing Bisphosphonates trial: a pilot study

Abstract

Purpose The comparative effectiveness of continuing or discontinuing long-term alendronate (ALN) on fractures is unknown. A large pragmatic ALN discontinuation study has potential to answer this question. Methods We conducted a 6-month pilot study of the planned The Effectiveness of DiscontinuinG bisphosphonatEs (EDGE) study among current long-term ALN users (women aged ≥65 with ≥3 years of ALN use) to determine study work flow and feasibility including: evaluating the administrative aspects of trial conduct (e.g. time to contract, IRB approval); assessing rates of site and participant recruitment; and evaluating post-randomization outcomes, including adherence, bisphosphonate-associated adverse events, and participant and site satisfaction. We assessed outcomes 1 and 6 months after randomization. Results Nine sites participated, including 7 community-based medical practices, and 2 academic medical centers. On average (SD) contract execution took 3.4 (2.3) months and IRB approval took 13.9 (4.1) days. Sites recruited 27 participants (13 to continue ALN, and 14 to discontinue ALN). Over follow-up, 22% of participants did not adhere to their randomization assignment: 30.8% in the continuation arm and 14.3% in the discontinuation arm. No fractures or adverse events were reported. Sites reported no issues regarding work flow, and participants were highly satisfied with the study. Conclusions Administrative procedures of the EDGE study were generally feasible, with minimal disruption to clinic flow. In this convenience sample, participant recruitment was suboptimal across most practice sites. Accounting for low treatment arm adherence, a comprehensive recruitment approach will be needed to effectively achieve the scientific goals of the EDGE study.

Medical Treatment for Osteoporosis: From Molecular to Clinical Opinions

“…Because the comparative effectiveness of continuing or discontinuing long-term alendronate on fractures is unknown, Wright et al conducted a six-month pilot study among current long-term alendronate users (women aged ≥65 with ≥three-year use) to evaluate outcomes one and six months after randomization, including adherence and bisphosphonate-associated adverse events [43]. For 27 participants (13 to continue alendronate, and 14 to discontinue alendronate), 22% of participants did not adhere to their randomization assignment: 30.8% in the continuation arm and 14.3% in the discontinuation arm.…”

“…For 27 participants (13 to continue alendronate, and 14 to discontinue alendronate), 22% of participants did not adhere to their randomization assignment: 30.8% in the continuation arm and 14.3% in the discontinuation arm. No fractures or adverse events were reported [43].…”

Atypical femur fractures: current understanding and approach to management

“…It is not, however, clear for how long a “drug holiday” is needed to reduce the risk of developing an AFF. 41 , 42 Fracture risk, and the need to restart osteoporosis medication, should be reassessed regularly while patients are on “drug holiday” from osteoporosis medication ( figure 4 ).…”

“…It is not, however, clear for how long a "drug holiday" is needed to reduce the risk of developing an AFF. 41,42 Fracture risk, and the need to restart osteoporosis medication, should be reassessed regularly while patients are on "drug holiday" from osteoporosis medication (figure 4). Those who are at highest risk for usual osteoporotic fractures, particularly those who have had vertebral or hip fractures, will generally benefit from continuing antiresorptive osteoporosis medication.…”

Tools and Methods for Real-World Evidence Generation

“…If a patient does not answer correctly, and assuming the consenting clinicians believe obtained true informed consent for this patient is indeed possible, the knowledge gap can sometimes be remediated, and the potential participant hyperlinked back to the relevant section of the informed consent document to refer back to the appropriate information in the informed consent document (Figure 3). Having pilot tested this assessment process during the development of a different pragmatic trial focused on bisphosphonate drug holidays (20), a focus group of IRB members as well as the IRBs governing the VERVE trial generally found it highly acceptable, particularly compared to the typical requirement that is generally satisfied (from a documentation standpoint) by a patient's initials appearing on the bottom of every page of the informed consent, and their signature at the end. The consent process can also entail any number of revisions or customizations required by a local IRB, or state and local regulations.…”