Perspective on optimizing clinical trials in critical care: how to puzzle out recurrent failures

Abstract

BackgroundCritical care is a complex field of medicine, especially because of its diversity and unpredictability. Mortality rates of the diseases are usually high and patients are critically ill, admitted in emergency, and often have several overlapping diseases. This makes research in critical care also complex because of patients’ conditions and because of the numerous ethical and regulatory requirements and increasing global competition. Many clinical trials in critical care have thus failed and almost no drug has yet been developed to treat intensive care unit (ICU) patients. Learning from the failures, clinical trials must now be optimized.Main bodySeveral aspects can be improved, beginning with the design of studies that should take into account patients’ diversity in the ICU. At the site level, selection should reflect more accurately the potential of recruitment. Management of all players that can be involved in the research at a site level should be a priority. Moreover, training should be offered to all staff members, including the youngest. National and international networks are also part of the future as they create a collective synergy potentially improving the efficacy of sites. Finally, computerization is another area that must be further developed with the appropriate tools.ConclusionClinical research in the ICU is thus a discipline in its own right that still requires tailored approaches. Changes have to be initiated by the investigators themselves as they know all the specificities of the field.

Does asymmetry in patient recruitment in large critical care trials follow the Pareto principle?

“…10 Australia New Zealand Intensive Care Research Centre, Melbourne, Australia. 11 Intensive Care Unit, Wesley Hospital, Brisbane, Australia. 12 Intensive Care Unit, Princess Alexandra Hospital, Brisbane, Australia.…”

“…In oncology trials conducted in North America, academic centres have been reported to enrol more patients than rural and regional centres, and most of the patient recruitment occurs from a small number of sites. In these trials, the pattern of recruitment reflected the Pareto principle or the "80/20" rule [10,11], which states that 80% of the effects arise from 20% of the causes. This principle was first described by an Italian economist, Vilfredo Pareto, who observed that 80% of the land in Italy was owned by 20% of the population and later noted that the same was applicable to other phenomena [12][13][14].…”

Heparin – Messias or Verschlimmbesserung?

“…To confound matters further, bleeding is common in the critically ill, 100 and performing clinical trials in critical care is fraught with challenges 101 . Balancing treatments affecting hemostasis in such unwell patients is often extremely difficult, and harder still to conduct in a rigorous, randomized manner enabling firm conclusions to be drawn.…”

Optimisation of the organ donor and effects on transplanted organs: a narrative review on current practice and future directions

“…Working with resources such as a QUOD and learning from their expertise will be important when supporting mechanistic research of organ donor management. Some of the suggestions to improve recruitment in ICU can be directly translated, whilst other areas require further feasibility work and qualitative research involving donor families, clinical staff and recipients. Looking outside of Europe, we are likely to learn important lessons from a national observational study in Canada that has recently completed recruitment and was designed to describe current organ donation practices, evaluate the effectiveness of interventions and assessed the feasibility of future randomised trials.…”