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. 2022 Apr 29:16:1379.
doi: 10.3332/ecancer.2022.1379. eCollection 2022.

Timelines to initiate a phase III trial across the globe: a sub-analysis of the APHINITY trial

Maria Alice Franzoi  1   2 , Marion Procter  3 , Chris Twelves  4 , Noam Ponde  5 , Daniel Eiger  6 , Orianne Emond  7 , Emma Clark  7 , Damien Parlier  1 , Sébastien Guillaume  1 , Linda Reaby  8 , Evandro de Azambuja  1 , Jose Bines  9
Affiliations

Timelines to initiate a phase III trial across the globe: a sub-analysis of the APHINITY trial

Maria Alice Franzoi et al. Ecancermedicalscience. .

Abstract

Background: Geographic location and national income may influence access to innovation in healthcare. We aimed to study if geographical location and national income influenced the timelines to activate the global phase III APHINITY trial, evaluating adjuvant pertuzumab in patients with HER2-positive early breast cancer.

Methods: Time from regulatory authority (RA) submission to approval (RAA), time to Ethics Committee/Institutional Review Board (EC/IRB) approval, time from study approval by EC/IRB to first randomised patient and from first to last randomised patient were collected. Analyses were conducted grouping countries by geographical region or economic income classification.

Results: Forty-one countries (of 42) had data available regarding all relevant timelines. No statistical difference was observed between the time to RAA and geographical region (p = 0.47), although there was a trend to longer time to RAA in upper middle-income economies (p = 0.07). Except for time from first to last patient randomised, there was wide variation in timelines overall and within geographical regions and economic income groups.

Conclusions: Geographical location and income classification did not appear to be the major drivers influencing time for clinical trial activation. Wide variability in activation timelines within geographical regions and income groups exists and is worthy of further investigation.

Keywords: clinical trials; ethics committee/institutional review board; regulatory approval; trial activation timelines.

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Conflict of interest statement

MAF, OE, DP, SG and LR: none. CT: Travel grant, Roche; advisory board: AstraZeneca, Eisai, Daiichi Sankyo, MSD. Speaker: Pfizer and Eisai. MP: MP’s institution received funding from Roche in respect of the APHINITY trial. NP: advisory board: Lilly; contracted research: Novartis, AstraZeneca, Daichii Sankyo, Roche and Pfizer; speaker: Novartis, Lilly, AstraZeneca and Roche. DE: funding for his research fellowship (2018–2019): Novartis; speaker fee: Janssen; salary paid by Roche. EA: honoraria and/or advisory board from Roche/GNE, Novartis, Seattle Genetics, Zodiac and Libbs; travel grants from Roche/GNE and GSK/Novartis; research grant to my institution from Roche/GNE, Astra-Zeneca, GSK/Novartis and Servier. JB: travel expenses: AstraZeneca and Roche; consultant: AstraZeneca, Daiichi Sankyo, Genomic Health, Libbs, Lilly MSD, Novartis, Pfizer and Roche. EC: employee of Roche Products Ltd; issued patent: Uses for and article of manufacture including HER2 dimerisation inhibitor pertuzumab, 13/649591.

Figures

Figure 1.
Figure 1.. Timelines analysed in the APHINITY trial. A: Time to regulatory approval according to geographical region. B: Time to regulatory approval according to economic income group. C: Time interval from the first randomized patient in each country.
See this image and copyright information in PMC

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References

    1. Metzger-Filho O, Azambuja E, Bradbury I, et al. Analysis of regional timelines to set up a global phase III clinical trial in breast cancer: the adjuvant lapatinib and/or trastuzumab treatment optimization experience. Oncologist. 2013;18:134–140. doi: 10.1634/theoncologist.2012-0342. - DOI - PMC - PubMed
    1. Tang M, Joensuu H, Simes RJ, et al. Challenges of international oncology trial collaboration – a call to action. Br J Cancer. 2019;121:515–521. doi: 10.1038/s41416-019-0532-4. - DOI - PMC - PubMed
    1. Pocock S, Calvo G, Marrugat J, et al. International differences in treatment effect: do they really exist and why? Eur Heart J. 2013;34:1846–1852. doi: 10.1093/eurheartj/eht071. - DOI - PubMed
    1. Vose JM, Chuk MK, Giles F. Challenges in opening and enrolling patients in clinical trials. Am Soc Clin Oncol Educ Book. 2017;37:139–143. doi: 10.1200/EDBK_179807. - DOI - PubMed
    1. Barrios CH, Reinert T, Werutsky G. Global breast cancer research: moving forward. Am Soc Clin Oncol Educ Book. 2018;38:441–450. doi: 10.1200/EDBK_209183. - DOI - PubMed

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