Goyal P, Safford M, Hilmer SN, et al. N-of-1 Trials to Facilitate Evidence-Based Deprescribing: Rationale and Case Study [published online ahead of print, 2022 Jun 15]. Br J Clin Pharmacol. 2022;10.1111/bcp.15442. doi:10.1111/bcp.15442
Junior Investigator Intensive scholar Parag Goyal and a team of researchers recently published a narrative review on deprescribing-N-of-1 trials. N-of-1 trials compare treatment effects in an individual patient by following the same patient over multiple time periods, a clinical trial subtype known as ‘multiple-period crossover design experiments.’ While N-of-1 trials are typically used to compare medication class or dosage, the therapeutic precision associated with this type of trial is also well-suited to deprescribing research. Deprescribing-N-of-1 trials provide evidence on the impact of continuing or stopping treatment in an individual patient. Individual-level evidence may allay patient and physician concerns about discontinuing medication and involve the patient in the clinical decision-making process. Additionally, N-of-1 trials may evade the time constraints that represent a significant barrier to deprescribing in the clinic setting.
In this paper, Dr. Goyal and co-authors present a case example of deprescribing beta-blockers for patients with heart failure with preserved ejection fraction (HFpEF) through ongoing N-of-1 trials. The effects of beta-blockers on function or quality of life among patients with HFpEF are not well-known. Patient and physician concerns about stopping beta-blockers often hinder deprescribing efforts. To address this issue, the study team’s ongoing pilot N-of-1 trials compare continuing beta-blockers to deprescribing beta-blockers over four time periods in a randomized order. Dr. Goyal and his team determined that this type of trial has the potential to transform deprescribing practices through patient and physician confidence, quantifiable data, and shared decision making.
Dr. Goyal provides his key takeaways from the paper:
- N-of-1 trials are an excellent approach for:
- Comparing the effects of taking and not taking a medication and facilitating shared decision making.
- Generating individual-level evidence for deprescribing when evidence is uncertain
- Combatting several well-described barriers to deprescribing, at both the patient and physician level.
- Our current work is as follows:
- N-of-1 trial to deprescribe beta-blockers in heart failure with preserved ejection fraction
- Preparing to launch another deprescribing study in cardiac amyloidosis
- Exploring the role of N-of-1 trials for other cardiovascular (and non-cardiovascular) conditions
- In summary:
- N-of-1 trials could be a transformative strategy to address polypharmacy and improve the wellbeing of older adults with multiple chronic conditions and polypharmacy.
- As we generate evidence for the potential effectiveness of N-of-1 trials for the purposes of shared decision making and deprescribing, consideration of implementation strategies will become critical to advance this work.