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

Authors

  • Kristina Vermeersch Department of Respiratory Medicine, Ghent University Hospital, Ghent
  • Bénédicte Demeyere Ghent University Hospital
  • Karen Denaux Department of Respiratory Diseases, University Hospitals Leuven, Leuven
  • Katelijne De Nys Clinical Trial Centre, University Hospitals Leuven- KU Leuven, Leuven
  • Thierry Troosters Department of Rehabilitation Sciences, KU Leuven, Leuven
  • Guy G. Brusselle Department of Respiratory Medicine, Ghent University Hospital, Ghent
  • Wim Janssens Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven

DOI:

https://doi.org/10.18203/2349-3259.ijct20194652

Keywords:

Academic, Clinical research, RCT, Challenges, Burden, Pharmaceutical industry

Abstract

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.

Author Biographies

Kristina Vermeersch, Department of Respiratory Medicine, Ghent University Hospital, Ghent

Department of Chronic Diseases, Metabolism and Ageing

Bénédicte Demeyere, Ghent University Hospital

Department of Respiratory Medicine

Karen Denaux, Department of Respiratory Diseases, University Hospitals Leuven, Leuven

Department of Respiratory Diseases

Katelijne De Nys, Clinical Trial Centre, University Hospitals Leuven- KU Leuven, Leuven

Clinical Trial Centre

Thierry Troosters, Department of Rehabilitation Sciences, KU Leuven, Leuven

Department of Rehabilitation Sciences

Guy G. Brusselle, Department of Respiratory Medicine, Ghent University Hospital, Ghent

Department of Respiratory Medicine

Wim Janssens, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven

Department of Chronic Diseases, Metabolism and Ageing

References

Schlegl E, Ducournau P, Ruof J. Different weights of the evidence-based medicine triad in regulatory, health technology assessment, and clinical decision making. Pharmaceut Med. 2017;31(4):213-6.

Paterson DL. Determining research priorities for clinician-initiated trials in infectious diseases. Med J Aust. 2013;198(5):270-2.

Editors Applied Clinical Trials. Challenging times for noncommercial researchers. Appl Clin Trials. 2006:11-14.

Tunis SR, Stryer DB, Clancy CM. Practical clinical trials: increasing the value of clinical research for decision making in clinical and health policy. JAMA. 2003;290(12):1624-32.

Georgias C, Grunow A, Olderog M, May A, Paulus U. Academic investigator-initiated trials and the challenge of sponsor responsibility: the Cologne Sponsor Model. Clin Trials. 2012;9:781-7.

Ravinetto R, Tinto H, Diro E, Okebe J, Mahendradhata Y, Rijal S, et al. It is time to revise the international Good Clinical Practices guidelines: recommendations from non-commercial North-South collaborative trials. BMJ Glob Heal. 2016;1(3):e000122.

Vermeersch K, Gabrovska M, Deslypere G, Demedts IK, Slabbynck H, Aumann J, et al. The Belgian trial with azithromycin for acute COPD exacerbations requiring hospitalization: An investigator-initiated study protocol for a multicenter, randomized, double-blind, placebo-controlled trial. Int J COPD. 2016;11(1):687-96.

Vermeersch K, Gabrovska M, Aumann J, Demedts IK, Corhay JL, Marchand E, et al. Azithromycin during acute COPD exacerbations requiring hospitalization (bace): a multicentre, randomized, double-blind, placebo-controlled trial. Am J Respir Crit Care Med. 2019:31046405.

Ravinetto RM, Talisuna A, De Crop M, Loen H, Menten J, Van Overmeir C, et al. Challenges of non-commercial multicentre North-South collaborative clinical trials. Trop Med Int Heal. 2013;18(2):237-41.

Remuzzi G, Schieppati A, Boissel J-P, Garattini S, Horton R. Independent clinical research in Europe. Lancet (London, England). 2004;364:1723-6.

English RA, Lebovitz Y, Giffin RB. Transforming Clinical Research in the United States. Washington (DC): National Academies Press (US); 2010.

Mostert B, Vullings W, de Boer M. Impact analyse Programma Voor Toegepast Biomedisch Onderzoek (Vlaanderen), 2013. Available at http://www.technopolis-group.com/wp-content/uploads/2013/12/Eindrapportage-Impactanalyse-TBM-programma.pdf. Accessed 18 August 2019.

Aufenacker Th J, Bannenberg J, Van Geldere D, et al. Quality of a non-subsidised multicentre randomised trial in general hospitals; an audit. [Dutch] TT-Kwaliteit van een ongefinancierde multicentrische gerandomiseerde trial in niet-academische ziekenhuizen; een audit. Ned Tijdschr Geneeskd. 2006;150(24):1337-41.

Clark J, Tugwell P. Who cares about academic medicine? BMJ. 2004;329(7469):751-2.

Alliance for Biomedical Research in Europe. Recommendations of the Alliance for Biomedical Research in Europe (BioMed Alliance) for the EU’s Ninth Framework Programme for Research and Innovation (FP9), 2018. Available at https://www. biomedeurope.org/images/eu-. Accessed 18 August 2019.

https://www.biomedeurope.org/images/eupolicy /Recommendations_of_the_BioMed_Alliance_for_the_FP9.pdf. Accessed 21August 2019.

Lindner MD, Torralba KD, Khan NA. Scientific productivity: an exploratory study of metrics and incentives. PLoS One. 2018;13(4):1-16.

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Published

2019-10-19

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Original Research Articles