Publication:

Challenges and threats of investigator-initiated multicenter randomized controlled trials: the BACE trial experience

Background Investigator-initiated clinical research has become a complex environment. Increasing administrative tasks and costs, imposed by stringent regulatory demands, risk to reduce this creative, independent and indispensable research field. The objective of the present study was to illustrate the burden of non-scientific challenges associated with an investigator-initiated multicentre randomized controlled trial, based on the Belgian trial with azithromycin for Chronic obstructive pulmonary disease (COPD) Exacerbations requiring hospitalization (BACE) trial experience.

Methods The trial enrolled 301 patients with COPD, hospitalized for an acute exacerbation between 2014-2017, and assessed the potential of azithromycin, an off-patent antibiotic. Key experienced challenges were complemented with registry data from the Clinical Trial Centre of the University Hospital Leuven to outline the local clinical respiratory research field, quotations for the trial protocol obtained from 3 pharmaceutical companies to provide insight into the budget restraints and a participation survey to capture the consortium’s perspective.

Results 60% of the required sample size was enrolled. Key challenges included trial implementation, study drug and database management. Industry-initiated trials dominated the local research field (61%), whereas investigator-initiated prospective interventional and multicenter trials accounted for 19% and 13%, respectively. The triple quotation revealed the BACE trial to require 1.6 to 2.1-fold the amount when executed by the pharmaceutical industry. The survey identified the lack of a local study team as an important obstacle for participation, along with inadequate financial compensation and excessive administrative workload.

Conclusions Without an adaptation of current regulatory and funding policies to overcome non-scientific challenges, investigator-initiated clinical research is risking to further decline.