Toward responsible clinical n-of-1 strategies for rare diseases
Victoria Defelippe, Ghislaine J. M. W. van Thiel, Willem M. Otte, Roger E. G. Schutgens, Bas C. Stunnenberg, J. Helen Cross, Finbar O’Callaghan, Valentina De Giorgis, Floor E. Jansen, Emilio Perucca, Eva H. Brilstra, Kees P. J. Braun
Abstract
N-of-1 strategies can provide high-quality evidence of treatment efficacy at the individual level and optimize evidence-based selection of off-label treatments for patients with rare diseases. Given their design characteristics, n-of-1 strategies are considered to sit at the intersection between medical research and clinical care. Therefore, whether n-of-1 strategies should be governed by research or care regulations remains a debated issue. Here, we delineate differences between medical research and optimized clinical care, and distinguish the regulations which apply to either. We also set standards for responsible optimized clinical n-of-1 strategies with (off-label) treatments for rare diseases. Implementing clinical n-of-1 strategies as defined here could aid in optimized treatment selection for such diseases. Teaser: N-of-1 strategies are considered a hybrid between research and care; therefore, which regulations n-of-1 strategies must abide by remains a topic of debate. We set the standards for responsible n-of-1 approaches as optimized care.