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Publication - Dr Alexandra McAleenan

    Optimizing the design and analysis of clinical trials for antibacterials against multidrug-resistant organisms

    a white paper from COMBACTE's STAT-Net


    Kraker, MEd, Sommer, H, Velde, Fd, Gravestock, I, Weiss, E, McAleenan, A, Nikolakopoulos, S, Amit, O, Ashton, T, Beyersmann, J, Held, L, Lovering, AM, MacGowan, A, Mouton, JW, Timsit, J-F, Wilson, D, Wolkewitz, M, Bettiol, E, Dane, A & Harbarth, S, 2018, ‘Optimizing the design and analysis of clinical trials for antibacterials against multidrug-resistant organisms: a white paper from COMBACTE's STAT-Net’. Clinical Infectious Diseases.


    Innovations are urgently required for clinical development of antibacterials against multidrug-resistant organisms. Therefore, a European, public-private working group (STAT-Net; part of Combatting Bacterial Resistance in Europe [COMBACTE]), has reviewed and tested several innovative trials designs and analytical methods for randomized clinical trials, which has resulted in 8 recommendations. The first 3 focus on pharmacokinetic and pharmacodynamic modeling, emphasizing the pertinence of population-based pharmacokinetic models, regulatory procedures for the reassessment of old antibiotics, and rigorous quality improvement. Recommendations 4 and 5 address the need for more sensitive primary end points through the use of rank-based or time-dependent composite end points. Recommendation 6 relates to the applicability of hierarchical nested-trial designs, and the last 2 recommendations propose the incorporation of historical or concomitant trial data through Bayesian methods and/or platform trials. Although not all of these recommendations are directly applicable, they provide a solid, evidence-based approach to develop new, and established, antibacterials and address this public health challenge.

    Full details in the University publications repository