Mapping the methodological diversity of published drug discontinuation studies—a scoping review of study topics, objectives, and designs

Abstract

Background Trials evaluating drug discontinuation (drug discontinuation trials, DDTs) show a broad methodological spectrum. There are several specific methodological aspects in drug discontinuation trials (e.g., determination of research question; configuration of intervention; definition of outcomes). To verify this specifies, we did a scoping review about the study designs of drug discontinuation trials. Methods A systematic literature search in Medline (PubMed), The Cochrane Library, EMBASE, CINAHL, Web of Science, and PsycINFO was performed. In a two-step selection process, we identified DDTs, which evaluate the discontinuation of one or more long-term medication as the investigated intervention, by two independent reviewers. Besides bibliographic data, we extracted several parameters to describe the used study design of the included DDTs: motivation for DDT, initially treatment aim of the discontinued medication, study design, methods of discontinuation, follow-up times, number of study participants, and outcome parameter. Results Out of 12,132 records, we included 581 DDTs. The most common motivation for doing a DDT were expected side effects (48.8%), the motivation of proving the efficacy of medication (21.6%), or doubts on the expected benefit of the used medication (13.8%). The majority of the discontinued medication was initially prescribed to improve the prognosis of a chronic disease (60.4%) or to relieve symptoms (31%). The study designs of the trials showed a broad methodological spectrum. The minority of the drug discontinuation trials were randomized controlled trials (34%). Conclusion The results of this scoping review illustrates the need for an evidence-based methodological standard for planning and conducting drug discontinuation trials.

Observational studies to emulate randomized trials: Some real‐world barriers

“…Some randomized trials study the effects of weaning off medications, generally for questions of risk-benefit. 31 Examples include trials of withdrawal of antiepileptic drugs in patients in remission, 32 of azathioprine in ulcerative colitis, 33 of digoxin in patients with heart failure, 34 of ICS in patients with COPD, 35 of sitagliptin in patients with type 2 diabetes 36 and of prednisone in systemic lupus erythematosus. 37 These trials can be challenging to emulate for several reasons, with the main issues relating to the definition of drug withdrawal and to confounding.…”