Phase IV Drug Trials With a Canadian Site: A Comparison of Industry-Funded and Non-IndustryFunded Trials

Document Type : Short Communication

Authors

1 School of Health Policy and Management, York University, Toronto, ON, Canada

2 Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada

3 School of Journalism and Communication, Carleton University, Ottawa, ON, Canada

4 School of Public Policy & Administration, Carleton University, Ottawa, ON, Canada

5 School of Public Policy & Administration, Carleton University, Ottawa, ON, Canada

Abstract

Recent regulatory reforms have favored expedited drug marketing and increased reliance on Phase IV clinical trials for safety and efficacy assurance. This study, utilizing ClinicalTrials.gov, assesses the characteristics of Phase IV trials, with at least one site in Canada, examining those funded by industry sponsors and those lacking industry funding. Additionally, it compares the publication status of industry-funded and non-industry-funded trials through a manual review of the medical literature. Between 2000 and 2022, 864 Phase IV trials were completed, with 480 (55.6%) receiving industry funding and 384 (44.4%) funded solely by non-industry sources. Industry-funded clinical trials were larger (mean 204 enrollees versus 70), more likely to be international (57.7% versus 9.6%) and reported results more promptly (1.21 years after completion versus 1.85 years), yet both types shared similar designs, outcomes, and completion times. Publication rates were 81.8% for industry-funded and 65.8% for non-industry-funded trials. The ClinicalTrials. gov registry displayed 48 inaccuracies in publication associations, raising concerns about its accuracy. Our findings underscore the existing institutional limitations in ensuring comprehensive reporting and publication of Phase IV trial results funded by both industry and non-industry sources.

Keywords


  1. Health Canada. Guidance Document: Management of Drug Submissions and Applications. https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html. Accessed March 15, 2023.
  2. Government of Canada. Clinical Trials and Drug Safety. https://www.canada.ca/en/health-canada/services/clinical-trials.html. Accessed March 15, 2023.
  3. Health Canada. Guidance Document for Clinical Trial Sponsors: Clinical Trial Applications. https://www.canada.ca/content/dam/hc-sc/migration/hc-sc/dhp-mps/alt_formats/pdf/prodpharma/applic-demande/guide-ld/clini/ctdcta_ctddec-eng.pdf. Accessed March 15, 2023.
  4. Government of Canada. Health Canada’s Clinical Trials Database. https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/health-canada-clinical-trials-database.html. Accessed March 15, 2023.
  5. Health Canada. Draft Guidance Document Registration of Clinical Trials and Public Disclosure of Results. https://www.canada.ca/content/dam/hc-sc/documents/programs/consultation-registration-clinical-trials-public-disclosure-results-new-guidance-public-search-portal/overview/overview-eng.pdf. Updated February 23, 2023. Accessed July 27, 2023.
  6. Davis C, Lexchin J, Jefferson T, Gøtzsche P, McKee M. "Adaptive pathways" to drug authorisation: adapting to industry? BMJ. 2016;354:i4437. doi:1136/bmj.i4437
  7. Eren Vural I, Herder M, Graham JE. From sandbox to pandemic: agile reform of Canadian drug regulation. Health Policy. 2021;125(9):1115-1120. doi:1016/j.healthpol.2021.04.018
  8. Spelsberg A, Prugger C, Doshi P, et al. Contribution of industry funded post-marketing studies to drug safety: survey of notifications submitted to regulatory agencies. BMJ. 2017;356:j337. doi:1136/bmj.j337
  9. Health and Human Services Department. Clinical Trials Registration and Results Information Submission. https://clinicaltrials.gov/ct2/manage-recs/fdaaa#WhichTrialsMustBeRegistered. Accessed March 15, 2023.
  10. Chen R, Desai NR, Ross JS, et al. Publication and reporting of clinical trial results: cross sectional analysis across academic medical centers. BMJ. 2016;352:i637. doi:1136/bmj.i637
  11. World Health Organization. WHO Statement on Public Disclosure of Clinical Trial Results. https://www.who.int/news/item/09-04-2015-japan-primary-registries-network. Accessed March 19, 2023.
  12. Alayche M, Cobey KD, Ng JY, et al. Evaluating prospective study registration and result reporting of trials conducted in Canada from 2009-2019. medRxiv [Preprint]. September 2, 2022. Available from: https://www.medrxiv.org/content/10.1101/2022.09.01.22279512v1.
  13. Bourgeois FT, Murthy S, Mandl KD. Outcome reporting among drug trials registered in ClinicalTrials.gov. Ann Intern Med. 2010;153(3):158-166. doi:7326/0003-4819-153-3-201008030-00006
  14. Hoffmann JM, Grossmann R, Widmann A. Academic clinical trials: publication of study results on an international registry-we can do better! Front Med (Lausanne). 2022;9:1069933. doi:3389/fmed.2022.1069933
  15. DeVito NJ, Bacon S, Goldacre B. Compliance with legal requirement to report clinical trial results on ClinicalTrials.gov: a cohort study. Lancet. 2020;395(10221):361-369. doi:1016/s0140-6736(19)33220-9
  16. Piller C. Failure to Report: A STAT Investigation of Clinical Trials Reporting. STAT. https://www.statnews.com/2015/12/13/clinical-trials-investigation/. Updated December 13, 2015. Accessed July 27, 2023.
  17. Zwierzyna M, Davies M, Hingorani AD, Hunter J. Clinical trial design and dissemination: comprehensive analysis of ClinicalTrials.gov and PubMed data since 2005. BMJ. 2018;361:k2130. doi:1136/bmj.k2130
  18. Nelson JT, Tse T, Puplampu-Dove Y, Golfinopoulos E, Zarin DA. Comparison of availability of trial results in ClinicalTrials.gov and PubMed by data source and funder type. JAMA. 2023;329(16):1404-1406. doi:1001/jama.2023.2351
  19. Ross JS, Tse T, Zarin DA, Xu H, Zhou L, Krumholz HM. Publication of NIH funded trials registered in ClinicalTrials.gov: cross sectional analysis. BMJ. 2012;344:d7292. doi:1136/bmj.d7292
  20. Ross JS, Mulvey GK, Hines EM, Nissen SE, Krumholz HM. Trial publication after registration in ClinicalTrials.gov: a cross-sectional analysis. PLoS Med. 2009;6(9):e1000144. doi:1371/journal.pmed.1000144
  21. The Economist. Spilling the Beans. The Economist; 2015:62-63.
  22. Morrow RL, Mintzes B, Gray G, Law MR, Garrison S, Dormuth CR. industry sponsor influence in clinical trial reporting in Canada: a qualitative interview study. Clin Ther. 2022;44(3):374-388. doi:1016/j.clinthera.2021.11.019
  23. Lundh A, Lexchin J, Mintzes B, Schroll JB, Bero L. Industry sponsorship and research outcome. Cochrane Database Syst Rev. 2017;2(2):MR000033. doi:1002/14651858.MR000033.pub3
  24. Hartung DM, Zarin DA, Guise JM, McDonagh M, Paynter R, Helfand M. Reporting discrepancies between the ClinicalTrials.gov results database and peer-reviewed publications. Ann Intern Med. 2014;160(7):477-483. doi:7326/m13-0480
  25. Riveros C, Dechartres A, Perrodeau E, Haneef R, Boutron I, Ravaud P. Timing and completeness of trial results posted at ClinicalTrials.gov and published in journals. PLoS Med. 2013;10(12):e1001566; discussion e1001566. doi:1371/journal.pmed.1001566
  26. Paludan-Müller AS, Créquit P, Boutron I. Reporting of harms in oncological clinical study reports submitted to the European Medicines Agency compared to trial registries and publications-a methodological review. BMC Med. 2021;19(1):88. doi:1186/s12916-021-01955-0
  27. Wieseler B, Wolfram N, McGauran N, et al. Completeness of reporting of patient-relevant clinical trial outcomes: comparison of unpublished clinical study reports with publicly available data. PLoS Med. 2013;10(10):e1001526. doi:1371/journal.pmed.1001526
  • Receive Date: 09 August 2023
  • Revise Date: 23 November 2023
  • Accept Date: 11 March 2024
  • First Publish Date: 13 March 2024