Browse/search for people

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

    Citation

    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.

    Abstract

    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