Is It TIME for More Research on Time-Limited Trials in Critical Care?

We would like to thank Downer et al1Downer K. Gustin J. Lincoln T. Goodman L. Barnett M.D. Communicating about time-limited trials.Chest. 2022; 161: 202-207Abstract Full Text Full Text PDF PubMed Google Scholar for providing structure and clarity for conversations about time-limited trials (TLT) in their article published in CHEST (January 2022). In situations of substantial prognostic uncertainty, the TLT can be an important way to implement the care that is best aligned with individual goals and preferences. To this end, physicians need to gain and maintain the trust of patients and families by providing rigorous assessments of the critical condition. Predictive assessments, however, are a weak spot in defining the specific parameters of a TLT. The fact that the physicians’ expertise in prognosticating outcome is limited2Meadow W. Pohlman A. Frain L. et al.Power and limitations of daily prognostications of death in the medical intensive care unit.Crit Care Med. 2011; 39: 474-479Crossref PubMed Scopus (83) Google Scholar is already acknowledged by discussing the TLT. Determining the appropriate timeframe for the TLT constitutes the first major challenge. Apart from statistical models designed for specific patient populations,3Shrime M.G. Ferket B.S. Scott D.J. et al.Time-limited trials of intensive care for critically ill patients with cancer.JAMA Oncol. 2016; 2: 76-83Crossref PubMed Scopus (54) Google Scholar no evidence-based solution to that problem exists, and the duration of the TLT still depends on the variable judgment of physicians. Moreover, during the TLT, additional information about organ function may fail to reduce prognostic uncertainty, especially about reaching the goals for quality of life in patients who are old and patients with multiple morbidities. Thus, decision-making at the end of the TLT can face greater uncertainty about the goal-concordance of care than at its beginning. Perpetuating this problem by repeating the TLT without adjustments would contradict the raison d’etre of this concept. The alternative, withdrawing life-sustaining treatment, is more than questionable in a situation of enhanced uncertainty. These problems and dilemmas underline the urgent need for further research into selecting the right patients for a TLT as well as how to plan and conduct TLTs. The mnemonic TIME suggested by Downer et al1Downer K. Gustin J. Lincoln T. Goodman L. Barnett M.D. Communicating about time-limited trials.Chest. 2022; 161: 202-207Abstract Full Text Full Text PDF PubMed Google Scholar offers excellent guidance for that purpose. In addition to recognizing and communicating prognostic uncertainty on admission (step ‘T’—truth about uncertainty), we need to better understand the evolution of uncertainty during critical care4Klein Klouwenberg P.M.C. Spitoni C. van der Poll T. Bonten M.J. Cremer O.L. MARS consortium. Predicting the clinical trajectory in critically ill patients with sepsis.Crit Care. 2019; 23: 408Crossref PubMed Scopus (7) Google Scholar to facilitate step ‘I’ (interval of time) and support step ‘M’ (measurement of improvement). The final step, ‘E’ (end or extend) involves the complex challenges of decision-making under uncertainty, which have been extensively studied in the field of behavioral economics. In particular, models based on prospect theory can incorporate personal reference points for quality of life and biases, such as risk aversion, to adjust decisions to the individual patient.5Lipman S.A. Brouwer W.B.F. Attema A.E. QALYs without bias? Nonparametric correction of time trade-off and standard gamble weights based on prospect theory.Health Econ. 2019; 28: 843-854Crossref PubMed Scopus (13) Google Scholar Eventually, these approaches can help to assure families and physicians that the best evidence has been taken into account to make an optimal decision for the patient. Communicating About Time-Limited TrialsCHESTVol. 161Issue 1PreviewTime-limited trials (TLTs) are used in the management of critical care patients undergoing potentially nonbeneficial interventions to improve prognostication and build trust and consensus between family and intensivists. When these trials are not well defined and executed, discordant views of the patient’s prognosis, conflict, and continuation of nonbeneficial care can arise. The mnemonic TIME (truth about uncertainty in prognosis, interval of time, measurement of improvement, and end or extend) can help facilitate clear communication surrounding TLTs. Full-Text PDF ResponseCHESTVol. 161Issue 6PreviewWe are delighted that Beil et al found our article to be a helpful construct and wholeheartedly agree it is time for more research into time-limited trials (TLTs).1 In a sense, every patient admitted to the ICU is undergoing an implicit TLT because the nature of medicine is to anticipate a certain clinical course and reassess whether complications or new findings arise. We advocate for explicit transparency with surrogates about the expected time course and the inherent uncertainty in the illness trajectory as a means to mitigate the perception that clinicians have abruptly “given up” when the patient does not improve as was hoped. Full-Text PDF